References on the Administration of Antipsychotic Agents Using ALZET^® Osmotic Pumps

1. Chlorpromazine

P2717 Konings,P.N.M., Culling-Berglund,A., Davis,T.P. Chronic haloperidol and chlorpromazine treatment alters in vitro B-endorphin metabolism in rat brain. Eur.J.Pharmacol. 1990; 191(--):115-128. >>> Haloperidol; Chlorpromazine; Saline, sterile; SC; rat; 2001; 2ML1; 8 days; controls received mp w/ vehicle.

P1348 Myschuk,T.N., Sawich,C.L., Allen,G. Long term (1 week) tranquilization of mice using Alzet(R) mini-osmotic pumps. Can.Lab Anim.Sci.News 1987; 20(-1-):18-20. >>> Chlorpromazine HCl; IP; SC; mice; 2002; 7, 10 days; complications with sc delivery; no stress/stress.

P1137 Davis,T.P., Culling-Berglund,A. Neuroleptic drug treatment alters in vitro central neurotensin metabolism. Psychoneuroendocrinology 1987; 12(-4-):253-260. >>> Chlorpromazine; Haloperidol; SC; rat; 2001; 2ML1; 8 days; controls received sham op; concomitant infusion of agents; comparison of agents effects; functionality of mp verified by gravimetric analyses.

P0908 Frey,P. Changes in cholecystokinin content in rat brain after subchronic treatment with neuroleptics. Ann.N.Y.Acad.Sci. 1985; 448(--):601-603. >>> Flupenthixol, cis-; Flupenthixol, trans-; Amitriptyline; Amphetamine; Atropine; Chlorpromazine; Clozapine; Fluphenazine; Haloperidol; Morphine; Prazosin; SC; rat; 2 weeks; mp model not stated; comparison of sc injections vs. mp infusion; antihypertensive.

P0447 Davis,T.P., Schoemaker,H., Culling,A.J. Centrally acting drugs alter in vitro B-endorphin processing in the rat. Eur.J.Pharmacol. 1984; 100(--):249-251. >>> Chlorpromazine; haloperidol; phenobarbital; promethazine; SC; Rat; 2001; 8 days; Comparison of agents effects.

P0385 Frey,P. Cholecystokinin octapeptide levels in rat brain are changed after subchronic neuroleptic treatment. Eur.J.Pharmacol. 1983; 95(--):87-92. >>> Chlorpromazine; Clozapine; Haloperidol; HCl; Saline; SC; rat; 2ML2; 2ML4; 2 and 4 weeks; comparison of single injec vs. infusion; comparison of agents effects; Hal. given for 2&4 weeks, Chlor.&Cloz. for 2 weeks; saline&HCl vehicle used w/Cloz., others used saline only; stability of Hal., Chlor.&Cloz. by TLC.

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2. Clozapine

P6686 Semenova,S., Markou,A. Clozapine treatment attenuated somatic and affective signs of nicotine and amphetamine withdrawal in subsets of rats exhibiting hyposensitivity to the initial effects of clozapine. Biological Psychiatry 2003; 54(-11-):1249-1264. >>> Nicotine tartrate; amphetamine; clozapine; HCL; saline; SC; Rat; 2ML1; 7,14 days; Controls received mp w/ vehicle; pumps replaced every 7 days for the 14 day study infusing clozapine; dependence; "in this experiment involving three pump implantations each pump was placed in a different part of the rats' body (left or right side of the back of the animal or at the shoulder area)." p. 1252; behavioral study.

P6201 Cochran,S.M., Kennedy,M., McKerchar,C.E., Steward,L.J., Pratt,J.A., Morris,B.J. Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: Differential modulation by antipsychotic drugs. Neuropsychopharmacology 2003; 28(-2-):265-275. >>> Clozapine; haloperidol; Acetic acid, glacial; water; SC; Rat; 2ML4; 21 days; Controls received mp w/ vehicle.

P6169 Kapur,S, Susan C. Antipsychotic Dosing in Preclinical Models is Often Unrepresentative of the Clinical Condition: A Suggested Solution Based on in Vivo Occupancy. Journal of Pharmacology and Experimental Therapeutics 2003; 305(-2-):625-631. >>> Haloperidol; olanzapine; risperidone; quetiapine; clozapine; Water; acetic acid, glacial; SC; Rat; 2ML2; 7 days; Plasma levels taken; dose-response (p. 629); comparison of daily injections vs. chronic mp; half-life (p. 626) 2-4 hours; haloperidol and risperidone were dissolved in distilled water; olanzapine, quetiapine and clozapine were dissolved in 1% to 2% acetic acid; great dose information; "we propose that only administration by pump (or administration more than four times a day[injections]) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone." p. 630.

P2833 Merchant,K.M., Dobie,D.J., Filloux,F.M., Totzke,M., Aravagiri,M., Dorsa,D.M. Effects of chronic haloperidol and clozapine treatment on neurotensin and c-fos mRNA in rat neostriatal subregions. J.Pharmacol.Exp.Ther. 1994; 271(-1-):460-471. >>> Haloperidol; Clozapine; SC; rat; 2ML2; 28 days; controls received mp with saline; pumps replaced at 14 days.

P1706 See,R.E., Ellison,G. Comparison of chronic administration of haloperidol and the atypical neuroleptics, clozapine and raclopride, in an animal model of tardive dyskinesia. Eur.J.Pharmacol. 1990; 181(--):175-186. >>> Clozapine; Haloperidol; Raclopride; Acetic acid, glacial; HCl; Sodium hydroxide; Water; SC; rat; 2ML4; 28 days; controls received an empty plastic pellet of identical size.

P0908 Frey,P. Changes in cholecystokinin content in rat brain after subchronic treatment with neuroleptics. Ann.N.Y.Acad.Sci. 1985; 448(--):601-603. >>> Flupenthixol, cis-; Flupenthixol, trans-; Amitriptyline; Amphetamine; Atropine; Chlorpromazine; Clozapine; Fluphenazine; Haloperidol; Morphine; Prazosin; SC; rat; 2 weeks; mp model not stated; comparison of sc injections vs. mp infusion; antihypertensive.

P0385 Frey,P. Cholecystokinin octapeptide levels in rat brain are changed after subchronic neuroleptic treatment. Eur.J.Pharmacol. 1983; 95(--):87-92. >>> Chlorpromazine; Clozapine; Haloperidol; HCl; Saline; SC; rat; 2ML2; 2ML4; 2 and 4 weeks; comparison of single injec vs. infusion; comparison of agents effects; Hal. given for 2&4 weeks, Chlor.&Cloz. for 2 weeks; saline&HCl vehicle used w/Cloz., others used saline only; stability of Hal., Chlor.&Cloz. by TLC.

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3. Fluphenazine

P0908 Frey,P. Changes in cholecystokinin content in rat brain after subchronic treatment with neuroleptics. Ann.N.Y.Acad.Sci. 1985; 448(--):601-603. >>> Flupenthixol, cis-; Flupenthixol, trans-; Amitriptyline; Amphetamine; Atropine; Chlorpromazine; Clozapine; Fluphenazine; Haloperidol; Morphine; Prazosin; SC; rat; 2 weeks; mp model not stated; comparison of sc injections vs. mp infusion; antihypertensive.

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4. Haloperidol

P9083 Samaha,A.N., Reckless,G.E., Seeman,P., Diwan,M., Nobrega,J.N., Kapur,S. Less is more: Antipsychotic drug effects are greater with transient rather than continuous delivery. Biological Psychiatry 2008; 64(-2-):145-152. >>> Haloperidol; Acetic acid, glacial; water; SC; Rat; 2ML2; 19 days; Comparison of SC injections vs. mp; animal info (male, Sprague Dawley, 225-250 g.); behavioral testing (conditioned avoidance).

P8543 Rasmussen,K., Hsu,M.A., Yang,Y.L. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: Implications for antipsychotic therapy. Neuropsychopharmacology 2007; 32(-4-):786-792. >>> Olanzapine; haloperidol; Water, distilled; sodium hydroxide; lactic acid; SC; Rat; 2ML2; 21 days; Controls received mp w/ vehicle; pumps replaced after 2 weeks; animal info (male, Sprague-Dawley, 280-330 grams).

P8434 Samaha,A.N., Seeman,P., Stewart,J., Rajabi,H., Kapur,S. "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time. Journal of Neuroscience 2007; 27(-11-):2979-2986. >>> Haloperidol; olanzapine; Acetic acid, glacial; water; NaOH; SC; Rat; 2ML2; 2,12,13 days; Controls received mp w/ vehicle; dose-response (fig. 4); comparison of SC injections vs. mp; half-life (p. 2985), 24 hours in humans, 1.4 hours in rats; tolerance; animal info (male, Sprague-Dawley, 225-250 grams); "Animal studies that use a mode of drug administration that more closely mimics clinical antipsychotic treatment (i.e., relatively continuous treatment) might be more informative about the true effects of these drugs in humans." (p. 2985).

P8279 Lin,E.J.D., Lee,N.J., Slack,K., Karl,T., Duffy,L., O'Brien,E., Matsumoto,I., Dedova,I., Herzog,H., Sainsbury,A. Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats. Neuropharmacology 2006; 51(-7-8-):1129-1136. >>> Haloperidol; risperidone; Acetic acid; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; no stress (see pg. 1131); half-life (p. 1131) 4-6 times shorter in rodents than in humans; post op. care (bupivicaine); animal info (male, Sprague-Dawley, 9-10 weeks old, 280-430 grams); "This dosing regimen also takes into consideration the reported 4-6 times shorter half-life of antipsychotic drugs in rodents than humans and highlights the advantage of using minipumps in the present study for continuous drug administration to achieve receptor occupancies comparable to clinical use in humans." (p. 1131).

P7448 Li,M., Budin,R., Fleming,A.S., Kapur,S. Effects of chronic typical and atypical antipsychotic drug treatment on maternal behavior in rats. SCHIZOPHRENIA RESEARCH 2005; 75(-2-3-):325-336. >>> Haloperidol; olanzapine; Water, double distilled; acetic acid, glacial; SC; Rat; 2ML4; 3 weeks; Controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; comparison of daily SC injections vs. mp; tolerance; animal info (female, Sprague-Dawley, 60-100 day old, postpartum, 250-380 g).

P7421 Siegel,S.J., Maxwell,C.R., Majumdar,S., Trief,D.F., Lerman,C., Gur,R.E., Kanes,S.J., Liang,Y. Monoamine reuptake inhibition and nicotine receptor antagonism reduce amplitude and gating of auditory evoked potentials. Neuroscience 2005; 133(-3-):729-738. >>> Bupropion, HCL; haloperidol; Water; SC; Mice; 1002; 12 days; Controls received mp w/ vehicle; animal info (C57BL/6J, 10-16 weeks old).

P7334 Turrone,P., Remington,G., Kapur,S., Nobrega,J.N. Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats. Biological Psychiatry 2005; 57(-4-):406-411. >>> Haloperidol; olanzapine; SC; Rat; 2ML4; 8 weeks; Controls received mp w/ vehicle; comparison of injections vs. mp; long-term study; pumps replaced every four weeks in a new incision; post op. care (placed in heated plexiglass cage); wound clips and vetbond were used to close incision.

P7312 Zhou,R., Gray,N.A., Yuan,P.X., Li,X.X., Chen,J.S., Chen,G., mschroder-Williams,P., Du,J., Zhang,L., Manji,H.K. The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long-term target for the actions of mood stabilizers. Journal of Neuroscience 2005; 25(-18-):4493-4502. >>> Amphetamine; fluvoxamine; haloperidol; Water; ethanol; SC; Rat; 2ML4; 3 weeks; Functionality of mp verified by residual volume; 50% ethanol used [not suggested by ALZET].

P7254 Kippin,T.E., Kapur,S., van der Kooy,D. Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. Journal of Neuroscience 2005; 25(-24-):5815-5823. >>> Haloperidol; domperidone; water, distilled; saline; SC; Rat; mice; 1002; 2ML2; 2ML4; 14, 30 days; Controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; dose-response (fig. 1); comparison of ip injections vs. mp; dopamine D2 receptor antagonist.

P6604 Marino,M.J., Awad-Granko,H., Ciombor,K.J., Conn,P.J. Haloperidol-induced alteration in the physiological actions of group I mGlus in the subthalamic nucleus and the substantia nigra pars reticulata. Neuropharmacology 2002; 43(-2-):147-159. >>> Haloperidol; Lactic acid; NaOH; saline; SC; Rat (neonate); 2001; 16 hours; Cyanoacrylate adhesive applied over sutures; animal info (15-18 days old, 20-37 grams).

P6365 Turrone,P., Remington,G., Kapur,S., Nobrega,J.N. Differential effects of within-day continuous vs transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats. Neuropsychopharmacology 2003; 28(-8-):1433-1439. >>> Haloperidol; SC; Rat; 2ML4; 8 weeks; Haloperidol plasma levels taken; comparison of SC injections vs. SC mp; long-term study; pumps replaced every 4 weeks; Vetbond glue and wound clips used to close wounds; "...minipump treated animals had stable haloperidol plasma levels throughout the day...subcutaneously [injection] treated rats experienced a dramatic decline over the same period." p. 1437.

P6201 Cochran,S.M., Kennedy,M., McKerchar,C.E., Steward,L.J., Pratt,J.A., Morris,B.J. Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: Differential modulation by antipsychotic drugs. Neuropsychopharmacology 2003; 28(-2-):265-275. >>> Clozapine; haloperidol; Acetic acid, glacial; water; SC; Rat; 2ML4; 21 days; Controls received mp w/ vehicle.

P6169 Kapur,S, Susan C. Antipsychotic Dosing in Preclinical Models is Often Unrepresentative of the Clinical Condition: A Suggested Solution Based on in Vivo Occupancy. Journal of Pharmacology and Experimental Therapeutics 2003; 305(-2-):625-631. >>> Haloperidol; olanzapine; risperidone; quetiapine; clozapine; Water; acetic acid, glacial; SC; Rat; 2ML2; 7 days; Plasma levels taken; dose-response (p. 629); comparison of daily injections vs. chronic mp; half-life (p. 626) 2-4 hours; haloperidol and risperidone were dissolved in distilled water; olanzapine, quetiapine and clozapine were dissolved in 1% to 2% acetic acid; great dose information; "we propose that only administration by pump (or administration more than four times a day[injections]) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone." p. 630.

P5292 Kaplan,G.B., Leite-Morris,K.A., Keith,D.J. Differential effects of treatment with typical and atypical antipsychotic drugs on adenylyl cyclase and G proteins. Neurosci.Lett. 1999/10/8; 273(-3-):147-150. >>> Haloperidol; Olanzapine; PEG; SC; Mice; 2002; 14 days; Controls received mp w/ vehicle; atypical antipsychotics; 2001 pump model listed, but release rate given as 0.5 ul/hr.

P4958 Powell,K.R., Iuvone,P.M., Holtzman,S.G. The role of dopamine in the locomotor stimulant effects and tolerance to these effects of caffeine. Pharmacology Biochemistry and Behavior 2001; 69(--):59-70. >>> Haloperidol; SC; rat; 2ML2; 14 days; controls received sham pumps; tolerance; caffeine tolerance.

P4835 Andersen,M.P., Pouzet,B. Effects of acute versus chronic treatment with typical or atypical antipsychotics on d-amphetamine-induced sensorimotor gating deficits in rats.. Psychopharmacology 2001; 156(--):291-304. >>> Haloperidol; Olanzapine; Sertindole;; Saline; HCl; Tartaric acid;; SC;; rat;; 2ML4;; 21 days;; Controls received mp w/ vehicle; functionality of mp verified by drug plasma levels (" ... the continuous infusion via mini-pumps is certainly the most relevant way to mimic conditions of treatment in clinic." p. 302); dose response (p. 302); comparison of SC injections vs. mp; half-life (p. 293); compared acute, subchronic (3 day) vs chronic (21 day) treatment; oral administration also examined; antipsychotics; schizophrenia; neurodegenerative (Huntington's disease); Olanzapine and sertindole were dissolved in a minimum amount of dilute HCl before dilution in saline; Haloperidol dissolved in minimal amount of dilute tartaric acid before final dilution in 0.9% saline;.

P4765 Martinez,Z.A., Oostwegel,J, Geyer,M.A., Ellison,G.D., Swerdlow,N.R. "Early" and "Late" effects of sustained haloperidol on apomorphine- and phencyclidine-induced sensorimotor gating deficits.. Neuropsychopharmacology 2000; 23(-5-):517-527. >>> Haloperidol;; Saline;; SC;; rat;; 28-day pump;; 28, 49 days;; Controls received mp w/ vehicle or sham pump; pumps replaced after 28 days; Schizophrenia; Haloperidol is a high-potency dopamine antagonist (D2 receptor); antipsychotic drugs; rats were housed singly to prevent excessive perturbation of the pumps; sham pumps consisted of silastic polymer pellets of approx. the same size and shape as minipumps..

P3459 Bergeron,R., de Montigny,C., Debonnel,G. Effect of short-term and long-term treatments with sigma ligands on the N-methyl-D-aspartate response in the CA(3) region of the rat dorsal hippocampus. Br.J.Pharmacol. 1997; 120(--):1351-1359. >>> Haloperidol; JO-1784; Pentazocine; DTG; SC; rat; 2-21 days; controls received mp w/saline; DTG is di(2-tolyl)guanidin.

P3085 Yamada,T., Hirayama,K., Kimura,H. Differential responses of noradrenaline and dopamine neurons in the mouse forebrain induced by continuous parenteral infusion of haloperidol. Eur.Neurol. 1991; 31(-Supl1-):28-33. >>> Haloperidol; Lactic acid; IP; mice; 2001; 1 week; controls received mp with vehicle; multiple pumps per animal (2).

P2833 Merchant,K.M., Dobie,D.J., Filloux,F.M., Totzke,M., Aravagiri,M., Dorsa,D.M. Effects of chronic haloperidol and clozapine treatment on neurotensin and c-fos mRNA in rat neostriatal subregions. J.Pharmacol.Exp.Ther. 1994; 271(-1-):460-471. >>> Haloperidol; Clozapine; SC; rat; 2ML2; 28 days; controls received mp with saline; pumps replaced at 14 days.

P2717 Konings,P.N.M., Culling-Berglund,A., Davis,T.P. Chronic haloperidol and chlorpromazine treatment alters in vitro B-endorphin metabolism in rat brain. Eur.J.Pharmacol. 1990; 191(--):115-128. >>> Haloperidol; Chlorpromazine; Saline, sterile; SC; rat; 2001; 2ML1; 8 days; controls received mp w/ vehicle.

P2611 Alberch,J., Arenas,E., Perez-Navarro,E., Marsal,J. Control of tachykinin-evoked acetylcholine release from rat striatal slices by dopaminergic neurons. Naunyn-Schmiedeberg's Arch.Pharmacol. 1993; 348(--):445-449. >>> Haloperidol; SCH-23390; SC; rat; 14 days; controls received mp w/ saline.

P2204 Ericson,H., Ross,S.B. Subchronic treatment of rats with remoxipride fails to modify sigma binding sites in the brain. Eur.J.Pharmacol.- Mol.Pharmacol.Sect. 1992; 226(--):157-161. >>> Remoxipride HCl; Haloperidol; Water; Acetic acid; SC; rat; 3,14 days; controls received sham operations.

P1802 See,R.E., Ellison,G. Intermittent and continuous haloperidol regimens produce different types of oral dyskinesias in rats. Psychopharmacology 1990; 100(--):404-412. >>> Haloperidol; Acetic acid; Sodium hydroxide; Water; SC; rat; 2ML4; 28 days; controls received an empty plastic pellet of identical size.

P1706 See,R.E., Ellison,G. Comparison of chronic administration of haloperidol and the atypical neuroleptics, clozapine and raclopride, in an animal model of tardive dyskinesia. Eur.J.Pharmacol. 1990; 181(--):175-186. >>> Clozapine; Haloperidol; Raclopride; Acetic acid, glacial; HCl; Sodium hydroxide; Water; SC; rat; 2ML4; 28 days; controls received an empty plastic pellet of identical size.

P1444 Ueda,H. Time course study of changes in the activity of rats during intraventricular infusion of 6-hydroxydopamine, haloperidol and sulpiride: a study of the relationship between an origin of the negative symptoms in schizophrenia and catecholamines. J.Iwate Med.Assoc. 1988; 40(-3-):385-398. >>> Dopamine, 6-hydroxy-; Haloperidol; Sulpiride; CSF/CNS; rat; 8 days; Japanese, English abstract.

P1345 Tanaka,M., Morimasa,T., Kaneyuki,T., Shohmori,T. Dopaminergic activity and met-enkephaline levels in the rat striatum after continuous treatment with various dopaminergic agents. Neuroscience 1988; 14(--):114-116. >>> Apomorphine; Haloperidol; Methamphetamine; SC; rat; 2 weeks; japanese with english abstract.

P1137 Davis,T.P., Culling-Berglund,A. Neuroleptic drug treatment alters in vitro central neurotensin metabolism. Psychoneuroendocrinology 1987; 12(-4-):253-260. >>> Chlorpromazine; Haloperidol; SC; rat; 2001; 2ML1; 8 days; controls received sham op; concomitant infusion of agents; comparison of agents effects; functionality of mp verified by gravimetric analyses.

P0908 Frey,P. Changes in cholecystokinin content in rat brain after subchronic treatment with neuroleptics. Ann.N.Y.Acad.Sci. 1985; 448(--):601-603. >>> Flupenthixol, cis-; Flupenthixol, trans-; Amitriptyline; Amphetamine; Atropine; Chlorpromazine; Clozapine; Fluphenazine; Haloperidol; Morphine; Prazosin; SC; rat; 2 weeks; mp model not stated; comparison of sc injections vs. mp infusion; antihypertensive.

P0838 Matsuda,L.A., Schmidt,C.J., Hanson,G.R., Gibb,J.W. Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase and tryptophan hydroxylase in rat. Neuropharmacology 1986; 25(-3-):249-255. >>> Haloperidol; MPTP; Water; SC; rat; 2ML1; 24 hours; same mp used in many animals; sc space around mp filled w/saline to facilitate pump action; controls received mp w/vehicle; see also P568.

P0813 McMillen,B.A. Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission. J.Neural Transm. 1985; 64(-1-):1-12. >>> Buspirone-HCl; Haloperidol; SC; rat; 2 weeks; mp model not stated; comparison of chronic administration in drinking water vs. mp infusion; stability of agent; toxicology.

P0623 McMillen,B.A. Acute and subchronic effects of MJ-13859, a potential antipsychotic drug, on rat brain dopaminergic function. J.Pharmacol.Exp.Ther. 1985; 233(-2-):369-375. >>> Haloperidol; MJ-13859; SC; rat; 2 weeks; mp model not stated; comparison of agents effects; comparison of ip or sc injection vs. mp infusion; controls had an incision only; 2 doses MJ-13859 infused; MJ-13859 is an antipsychotic.

P0595 George,S., Kertesz,M. Met-enkephalin concentrations in straitum respond reciprocally to alterations in dopamine neurotransmission. Peptides 1987; 8(-3-):487-492. >>> Apomorphine; FK-33824; Haloperidol; Naloxone; Ethanol; Tartaric acid; Water; SC; rat; 5, 9 days; mp model not stated; controls received mp w/unspecified vehicle or were sham-operated; agents infused separately w/appropriate vehicle; comparison of sc inject. vs. mp infusion.

P0556 Gysling,K., Beinfeld,M.C. Failure of chronic haloperidol treatment to alter levels of cholecystokinin in the rat brain striatum and olfactory tubercle-nucleus accumbens area. Neuropeptides 1984; 4(-5-):421-423. >>> Haloperidol; Saline; SC; rat; 2ML4; 2 weeks; comparison of daily sc injec vs. mp infusion; stability of residual Hal. verified by HPLC; peptides.

P0472 Joseph,J.A., Bartus,R.T., Clody,D., Morgan,D., Finch,C., Beer,B., Sesack,S. Psychomotor performance in the senescent rodent: reduction of deficits via striatal dopamine receptor up-regulation. Neurobiol.Aging 1983; 4(-4-):313-319. >>> Haloperidol; HCl; Water; SC; rat; 2 weeks; 2 pumps/animal.

P0465 Le Douarin,C., Fage,D., Scatton,B. Effects of cyclo (Leu-Gly) on neurochemical indices of striatal dopaminergic supersensitivity induced by prolonged haloperidol treatment. Life Sci. 1984; 34(-4-):393-399. >>> Haloperidol; SC; rat; 2002; 2 weeks; concomitant deliv. cyclo (Leu-Gly).

P0447 Davis,T.P., Schoemaker,H., Culling,A.J. Centrally acting drugs alter in vitro B-endorphin processing in the rat. Eur.J.Pharmacol. 1984; 100(--):249-251. >>> Chlorpromazine; haloperidol; phenobarbital; promethazine; SC; Rat; 2001; 8 days; Comparison of agents effects.

P0420 Scatton,B., Fage,D. Hypophysectomy fails to affect the supersensitivity of striatal dopamine target cells induced by prolonged haloperidol treatment. Eur.J.Pharmacol. 1984; 98(--):1-7. >>> Haloperidol; SC; rat; 2002; 2 weeks; no comment posted.

P0385 Frey,P. Cholecystokinin octapeptide levels in rat brain are changed after subchronic neuroleptic treatment. Eur.J.Pharmacol. 1983; 95(--):87-92. >>> Chlorpromazine; Clozapine; Haloperidol; HCl; Saline; SC; rat; 2ML2; 2ML4; 2 and 4 weeks; comparison of single injec vs. infusion; comparison of agents effects; Hal. given for 2&4 weeks, Chlor.&Cloz. for 2 weeks; saline&HCl vehicle used w/Cloz., others used saline only; stability of Hal., Chlor.&Cloz. by TLC.

P0371 Le Douarin,C., Oblin,A., Fage,D., Scatton,B. Influence of lithium on biochemical manifestations of striatal dopamine target cell supersensitivity induced by prolonged haloperidol treatment. Eur.J.Pharmacol. 1983; 93(--):55-62. >>> Haloperidol; SC; rat; 2002; 2 weeks; no comment posted.

P0301 Chang,R.S.L., Lotti,V.J., Martin,G.E., Chen,T.B. Increase in brain 125I-cholecystokinin (CCK) receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions. Life Sci. 1983; 32(--):871-878. >>> Haloperidol; SC; guinea-pig; mice; 2002; 2ML2; 8-21 days; 2002 in mice, 2ML2 in GP.

P0208 Kapetanovic,I.M., Sweeney,D.J., Rapoport,S.I. Age effects on haloperidol pharmacokinetics in male, Fischer-344 rats. J.Pharmacol.Exp.Ther. 1982; 221(-2-):434-438. >>> Haloperidol; Acetic acid; IP; rat; 4 days; comparison of bolus ip injection vs. infusion.

P0166 Login,I.S., Nagy,I., MacLeod,R.M. Restoration of pituitary prolactin synthesis and release by the administration of morphine to rats bearing a transplanted prolactin-secreting tumor. Neuroendocrinology 1981; 33(-2-):101-104. >>> Haloperidol; Morphine sulfate; Lactic acid; Saline; Water; SC; rat; 1701; 4 days; cancer.

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5. Olanzapine

P8067 Coccurello,R., Caprioli,A., Ghirardi,O., Conti,R., Ciani,B., Daniele,S., Bartolomucci,A., Moles,A. Chronic administration of olanzapine induces metabolic and food intake alterations: a mouse model of the atypical antipsychotic-associated adverse effects. Psychopharmacology 2006; 186(-4-):561-571. >>> Olanzapine; Saline, sterile isotonic; NoOH; acetic acid; SC; Mice; 2004; 4 weeks; Controls received mp w/ vehicle; dose-response (fig.3); comparison of oral gavage vs. mp; half-life (p.563) short in mice and rats; animal info (female, CD-1, 28g.); agent also known as LY170053; " Olanzapine was infused subcutaneously (s.c.) by osmotic mini-pumps, thus avoiding the stress-associated procedures of gavage administration." (p.562); mp primed overnight in 37 celsius saline.

P7995 Verma,V., Rasmussen,K., Dawe,G.S. Effects of short-term and chronic olanzapine treatment on immediate early gene protein and tyrosine hydroxylase immunoreactivity in the rat locus coeruleus and medial prefrontal cortex. Neuroscience 2006; 143(-2-):573-585. >>> Olanzapine; Saline; SC; Rat; 2ML2; 2ML4; 1, 2, 4 weeks; 4 hours; Controls received mp w/ vehicle; animal info (adult, male, Sprague-Dawley, 180-200 grams).

P7566 Seager,M.A., Barth,V.N., Phebus,L.A., Rasmussen,K. Chronic coadministration of olanzapine and fluoxetine activates locus coeruleus neurons in rats: implications for bipolar disorder. Psychopharmacology 2005; 181(-1-):126-133. >>> Olanzapine; Water, distilled; NaOH; lactic acid; SC; Rat; 2ML1; 3 weeks; Controls received mp w/ saline; dose-response (fig. 1); pumps replaced every week; half-life (pg.127); animal info (male, Sprague-Dawley 225-310 g); 5% lactic acid.

P7562 Hillebrand,J.J.G., van Elburg,A.A., Kas,M.J.H., van Engeland,H., Adan,R.A.H. Olanzapine reduces physical activity in rats exposed to activity-based anorexia: Possible implications for treatment of anorexia nervosa?. Biological Psychiatry 2005; 58(-8-):651-657. >>> Olanzapine; Saline, sterile isotonic; acetic acid; NaOH; SC; Rat; 2001; 1 week; Controls received mp w/ vehicle; half-life (pg. 655) 2.5 hours in rats, 21-53 hours in humans; post op. care (buprenorphin, saline fluid treatment); animal info (female, Wistar, 160 g); mp primed overnight at 37 C.

P7448 Li,M., Budin,R., Fleming,A.S., Kapur,S. Effects of chronic typical and atypical antipsychotic drug treatment on maternal behavior in rats. SCHIZOPHRENIA RESEARCH 2005; 75(-2-3-):325-336. >>> Haloperidol; olanzapine; Water, double distilled; acetic acid, glacial; SC; Rat; 2ML4; 3 weeks; Controls received mp w/ vehicle; functionality of mp verified by plasma drug levels; comparison of daily SC injections vs. mp; tolerance; animal info (female, Sprague-Dawley, 60-100 day old, postpartum, 250-380 g).

P7334 Turrone,P., Remington,G., Kapur,S., Nobrega,J.N. Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats. Biological Psychiatry 2005; 57(-4-):406-411. >>> Haloperidol; olanzapine; SC; Rat; 2ML4; 8 weeks; Controls received mp w/ vehicle; comparison of injections vs. mp; long-term study; pumps replaced every four weeks in a new incision; post op. care (placed in heated plexiglass cage); wound clips and vetbond were used to close incision.

P6911 Rasmussen,K., Benvenga,M.J., Bymaster,F.P., Calligaro,D.O., Cohen,I.R., Falcone,J.F., Hemrick-Luecke,S.K., Martin,F.M., Moore,N.A., Nisenbaum,L.K., Schaus,J.M., Sundquist,S.J., Tupper,D.E., Wiernicki,T.R., Nelson,D.L. Preclinical pharmacology of FMPD [6- fluoro-10-[ 3-( 2-methoxyethyl)- 4- methyl-piperazin-1-yl]-2-methyl-4H-3- thia-4,9-diaza-benzo[f]azulene]: A potential novel antipsychotic with lower histamine H1 receptor affinity than olanzapine. Journal of Pharmacology and Experimental Therapeutics 2005; 315(-3-):1265-1277. >>> FMPD; olanzapine, HCl; Water; SC; Rat; 2ML1; 2ML2; 14 days; Controls received mp w/ vehicle; post op. care (antibiotic ointment); animal info (male, Sprague-Dawley, 280-330 g); potential novel antipsychotic.

P6169 Kapur,S, Susan C. Antipsychotic Dosing in Preclinical Models is Often Unrepresentative of the Clinical Condition: A Suggested Solution Based on in Vivo Occupancy. Journal of Pharmacology and Experimental Therapeutics 2003; 305(-2-):625-631. >>> Haloperidol; olanzapine; risperidone; quetiapine; clozapine; Water; acetic acid, glacial; SC; Rat; 2ML2; 7 days; Plasma levels taken; dose-response (p. 629); comparison of daily injections vs. chronic mp; half-life (p. 626) 2-4 hours; haloperidol and risperidone were dissolved in distilled water; olanzapine, quetiapine and clozapine were dissolved in 1% to 2% acetic acid; great dose information; "we propose that only administration by pump (or administration more than four times a day[injections]) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone." p. 630.

P5912 Tarazi,F.I., Baldessarini,R.J., Kula,N.S., Zhang,K.H. Long-term effects of olanzapine, risperidone, and quetiapine on ionotropic glutamate receptor types: Implications for antipsychotic drug treatment. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-3-):1145-1151. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Functionality of mp verified by residual volume; antipsychotic drugs.

P5866 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of newer antipsychotic drugs on neuronal nitric oxide synthase in rat brain. NITRIC OXIDE-BIOLOGY AND CHEMISTRY 2002; 7(-4-):297-300. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Controls received mp w/ vehicle; antipsychotic agents.

P5122 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions. Psychopharmacology 2002; 161(--):263-270. >>> Olanzapine; Risperidone; Quetiapine fumarate; SC; rat; 4 weeks; controls received mp w/ vehicle; functionality of mp verified by residual volume; antipsychotic agents.

P4835 Andersen,M.P., Pouzet,B. Effects of acute versus chronic treatment with typical or atypical antipsychotics on d-amphetamine-induced sensorimotor gating deficits in rats.. Psychopharmacology 2001; 156(--):291-304. >>> Haloperidol; Olanzapine; Sertindole;; Saline; HCl; Tartaric acid;; SC;; rat;; 2ML4;; 21 days;; Controls received mp w/ vehicle; functionality of mp verified by drug plasma levels (" ... the continuous infusion via mini-pumps is certainly the most relevant way to mimic conditions of treatment in clinic." p. 302); dose response (p. 302); comparison of SC injections vs. mp; half-life (p. 293); compared acute, subchronic (3 day) vs chronic (21 day) treatment; oral administration also examined; antipsychotics; schizophrenia; neurodegenerative (Huntington's disease); Olanzapine and sertindole were dissolved in a minimum amount of dilute HCl before dilution in saline; Haloperidol dissolved in minimal amount of dilute tartaric acid before final dilution in 0.9% saline;.

P5292 Kaplan,G.B., Leite-Morris,K.A., Keith,D.J. Differential effects of treatment with typical and atypical antipsychotic drugs on adenylyl cyclase and G proteins. Neurosci.Lett. 1999/10/8; 273(-3-):147-150. >>> Haloperidol; Olanzapine; PEG; SC; Mice; 2002; 14 days; Controls received mp w/ vehicle; atypical antipsychotics; 2001 pump model listed, but release rate given as 0.5 ul/hr.

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6. Quetiapine

P6169 Kapur,S, Susan C. Antipsychotic Dosing in Preclinical Models is Often Unrepresentative of the Clinical Condition: A Suggested Solution Based on in Vivo Occupancy. Journal of Pharmacology and Experimental Therapeutics 2003; 305(-2-):625-631. >>> Haloperidol; olanzapine; risperidone; quetiapine; clozapine; Water; acetic acid, glacial; SC; Rat; 2ML2; 7 days; Plasma levels taken; dose-response (p. 629); comparison of daily injections vs. chronic mp; half-life (p. 626) 2-4 hours; haloperidol and risperidone were dissolved in distilled water; olanzapine, quetiapine and clozapine were dissolved in 1% to 2% acetic acid; great dose information; "we propose that only administration by pump (or administration more than four times a day[injections]) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone." p. 630.

P5912 Tarazi,F.I., Baldessarini,R.J., Kula,N.S., Zhang,K.H. Long-term effects of olanzapine, risperidone, and quetiapine on ionotropic glutamate receptor types: Implications for antipsychotic drug treatment. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-3-):1145-1151. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Functionality of mp verified by residual volume; antipsychotic drugs.

P5866 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of newer antipsychotic drugs on neuronal nitric oxide synthase in rat brain. NITRIC OXIDE-BIOLOGY AND CHEMISTRY 2002; 7(-4-):297-300. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Controls received mp w/ vehicle; antipsychotic agents.

P5122 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions. Psychopharmacology 2002; 161(--):263-270. >>> Olanzapine; Risperidone; Quetiapine fumarate; SC; rat; 4 weeks; controls received mp w/ vehicle; functionality of mp verified by residual volume; antipsychotic agents.

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7. Remoxipride HCl

P2736 Georgieva,J., Mohringe,B., Magnusson,O. Neurochemical effects of prolonged treatment with remoxipride as assessed by intracerebral microdialysis in freely moving rats. Prog.Neuro-Psychopharmacol.Biol.Psychiat. 1994; 18(--):1187-1201. >>> Remoxipride HCl; Sodium chloride; SC; rat; 2002; 14 days; controls received sodium chloride; functionality of mp verified by checking blood levels of drug and determining residual drug amount; comparison of sc injections vs mp; remoxipride is an antipsychotic drug.

P2204 Ericson,H., Ross,S.B. Subchronic treatment of rats with remoxipride fails to modify sigma binding sites in the brain. Eur.J.Pharmacol.- Mol.Pharmacol.Sect. 1992; 226(--):157-161. >>> Remoxipride HCl; Haloperidol; Water; Acetic acid; SC; rat; 3,14 days; controls received sham operations.

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8. Risperidone

P8279 Lin,E.J.D., Lee,N.J., Slack,K., Karl,T., Duffy,L., O'Brien,E., Matsumoto,I., Dedova,I., Herzog,H., Sainsbury,A. Distinct endocrine effects of chronic haloperidol or risperidone administration in male rats. Neuropharmacology 2006; 51(-7-8-):1129-1136. >>> Haloperidol; risperidone; Acetic acid; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; no stress (see pg. 1131); half-life (p. 1131) 4-6 times shorter in rodents than in humans; post op. care (bupivicaine); animal info (male, Sprague-Dawley, 9-10 weeks old, 280-430 grams); "This dosing regimen also takes into consideration the reported 4-6 times shorter half-life of antipsychotic drugs in rodents than humans and highlights the advantage of using minipumps in the present study for continuous drug administration to achieve receptor occupancies comparable to clinical use in humans." (p. 1131).

P8027 O'Brien,E., Dedova,I., Duffy,L., Cordwell,S., Karl,T., Matsumoto,I. Effects of chronic risperidone treatment on the striatal protein profiles in rats. Brain Research 2006; 1113(--):24-32. >>> Risperidone; Water, sterile; acetic acid; sodium hydroxide; SC; Rat; 2ML4; 28 days; Controls received mp w/ vehicle; animal info (Sprague-Dawley, male, 357 grams; 11 weeks old); behavioral study.

P6169 Kapur,S, Susan C. Antipsychotic Dosing in Preclinical Models is Often Unrepresentative of the Clinical Condition: A Suggested Solution Based on in Vivo Occupancy. Journal of Pharmacology and Experimental Therapeutics 2003; 305(-2-):625-631. >>> Haloperidol; olanzapine; risperidone; quetiapine; clozapine; Water; acetic acid, glacial; SC; Rat; 2ML2; 7 days; Plasma levels taken; dose-response (p. 629); comparison of daily injections vs. chronic mp; half-life (p. 626) 2-4 hours; haloperidol and risperidone were dissolved in distilled water; olanzapine, quetiapine and clozapine were dissolved in 1% to 2% acetic acid; great dose information; "we propose that only administration by pump (or administration more than four times a day[injections]) can provide clinical-like occupancies for haloperidol, olanzapine, and risperidone." p. 630.

P5912 Tarazi,F.I., Baldessarini,R.J., Kula,N.S., Zhang,K.H. Long-term effects of olanzapine, risperidone, and quetiapine on ionotropic glutamate receptor types: Implications for antipsychotic drug treatment. Journal of Pharmacology and Experimental Therapeutics 2003; 306(-3-):1145-1151. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Functionality of mp verified by residual volume; antipsychotic drugs.

P5866 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of newer antipsychotic drugs on neuronal nitric oxide synthase in rat brain. NITRIC OXIDE-BIOLOGY AND CHEMISTRY 2002; 7(-4-):297-300. >>> Olanzapine; risperidone; quetiapine fumerate; SC; Rat; 28 days; Controls received mp w/ vehicle; antipsychotic agents.

P5122 Tarazi,F.I., Zhang,K.H., Baldessarini,R.J. Long-term effects of olanzapine, risperidone, and quetiapine on serotonin 1A, 2A and 2C receptors in rat forebrain regions. Psychopharmacology 2002; 161(--):263-270. >>> Olanzapine; Risperidone; Quetiapine fumarate; SC; rat; 4 weeks; controls received mp w/ vehicle; functionality of mp verified by residual volume; antipsychotic agents.

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9. Spiperone

P1288 Shippenberg,T.S., Herz,A. Motivational effects of opioids; influence of D-1 versus D-2 receptors antagonists. Eur.J.Pharmacol. 1988; 151(--):233-242. >>> Spiperone; SCH-23390; DMSO; Water; SC; rat; 2001; 2ML1; 7 days; functionality of mp verified after delivery; dopamine antagonist.

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10. Sulpiride

P2115 Zhou,L.-W., Zhang,S.-P., Welsh,S., Connell,T.A., Weiss,B. Triazolam blocks the initial rotational effects of quinpirole but permits the later developing reduction of dopamine D2-mediated rotational behavior and dopamine D2 receptors. Eur.J.Pharmacol. 1992; 218(--):219-227. >>> Quinpirole HCl; Sulpiride; Triazolam; Ascorbic acid; DMSO; SC; mice; 2001; 6 days; Quinpirole is a dopamine agonist; antidepressant; stability verified in vitro for 7 days.

P1444 Ueda,H. Time course study of changes in the activity of rats during intraventricular infusion of 6-hydroxydopamine, haloperidol and sulpiride: a study of the relationship between an origin of the negative symptoms in schizophrenia and catecholamines. J.Iwate Med.Assoc. 1988; 40(-3-):385-398. >>> Dopamine, 6-hydroxy-; Haloperidol; Sulpiride; CSF/CNS; rat; 8 days; Japanese, English abstract.

P0630 Costall,B., Domeney,A.M., Naylor,R.J. The continuity of dopamine receptor antagonism can dictate the long-term behavioural consequences of a mesolimibic infusion of dopamine. Neuropharmacology 1985; 2(-3-):193-197. >>> Dopamine HCl; Sulpiride; Nitrogen; Sodium metabisulfite; CSF/CNS (nucleus accumbens); IP; rat; 13 days; mp model not stated; comparison of SULP ip injec vs. mp infusion; 2 mp/rat - bilateral infusion; mp primed overnight; vehicles listed used w/DOP; concomitant SULP admin. ip.

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11. Trifluoperazine

P0144 Dougherty Jr,G.G., Ellinwood Jr,E.H. Amphetamine behavioral toxicity: rotational behavior after chronic intrastriatal infusion. Biol.Psychiatry 1981; 16(-5-):479-488. >>> Trifluoperazine; Amphetamine sulfate, d-; Saline; CSF/CNS (corpus striatum); rat; 7 days; caudate putamen.

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