title: Evaluation of age and sex differences in locomotion and catalepsy during repeated administration of haloperidol and clozapine in adolescent and adult rats.
abstract: Adolescence is associated with characteristic behavioral patterns as well as with substantial neuronal pruning and re-organization of the brain. Recent research has determined that the effects of various centrally active drugs differ in adolescents and adults. This study examined the motor effects of two prototypic antipsychotics in adult [>postnatal day 70 (PN70)] and adolescent (PN30-PN39) rats. Rats were injected daily with saline, 0.3 mg/kg haloperidol, or 10 mg/kg clozapine for 10 days and activity and catalepsy were measured. Adolescents of both sexes were less sensitive to the cataleptic effects of haloperidol than were adults. Male adolescents were also less sensitive to the cataleptic effects of clozapine, although this difference was transitory. In contrast, female adults showed decreased sensitivity to clozapine's effects, differing from all other groups. These results suggest that adolescents of both sexes may be less sensitive to the extrapyramidal motor effects of haloperidol. Translational implications of the clozapine results are less clear; however, results suggest that developmental differences in neurochemical systems affected by clozapine that are also related to motor behavior may play a role. These results also emphasize the importance of age and sex as determinants of the pharmacological effects of these antipsychotics.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. jwiley@vcu.edu
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Wiley
authors.forename: Rhys L
authors.initials: RL
authors.lastname: Evans
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000523:psychology; D003024:Clozapine / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000523:psychology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012727:Sex Characteristics
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine; D006220:Haloperidol
references.citation: Neurosci Biobehav Rev. 2000 Jun;24(4):417-63
references.pmid: 10817843
references.citation: Psychopharmacology (Berl). 1983;81(3):239-43
references.pmid: 6417713
references.citation: Eur Neuropsychopharmacol. 2000 May;10(3):159-64
references.pmid: 10793317
references.citation: Schizophr Res. 2007 Aug;94(1-3):293-305
references.pmid: 17574821
references.citation: Psychopharmacology (Berl). 1999 Jan;141(3):267-78
references.pmid: 10027508
references.citation: Pharmacol Biochem Behav. 1993 Oct;46(2):405-9
references.pmid: 8265695
references.citation: Eur J Pharmacol. 2003 Jun 27;471(3):185-93
references.pmid: 12826237
references.citation: Psychopharmacology (Berl). 1981;73(3):219-22
references.pmid: 6787640
references.citation: Neuropsychopharmacology. 2006 Sep;31(9):1869-79
references.pmid: 16237379
references.citation: Psychopharmacology (Berl). 2006 Jul;186(4):579-86
references.pmid: 16758242
references.citation: Brain Res Mol Brain Res. 2002 Apr 30;100(1-2):75-83
references.pmid: 12008023
references.citation: Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73
references.pmid: 8935801
references.citation: Psychiatry Res. 1991 Aug;38(2):125-34
references.pmid: 1754627
references.citation: Psychoneuroendocrinology. 2002 Aug;27(6):683-91
references.pmid: 12084661
references.citation: Psychopharmacology (Berl). 1988;94(1):46-51
references.pmid: 2894702
references.citation: J Neurosci. 1985 Nov;5(11):2831-8
references.pmid: 4056856
references.citation: Eur J Pharmacol. 1992 Apr 29;215(1):29-34
references.pmid: 1355442
references.citation: Neurotoxicol Teratol. 2007 Jan-Feb;29(1):37-46
references.pmid: 17049207
references.citation: Brain Res Dev Brain Res. 2002 Sep 20;138(1):27-34
references.pmid: 12234655
references.citation: Psychiatr Clin North Am. 1993 Dec;16(4):779-91
references.pmid: 8309812
references.citation: Psychoneuroendocrinology. 1983;8(2):225-36
references.pmid: 6353470
references.citation: Neurochem Int. 1997 Mar;30(3):277-90
references.pmid: 9041559
references.citation: Psychopharmacology (Berl). 1984;82(4):406-8
references.pmid: 6427835
references.citation: Neuroreport. 1997 Apr 14;8(6):1495-8
references.pmid: 9172161
references.citation: Psychopharmacology (Berl). 1981;74(2):166-9
references.pmid: 6791221
references.citation: Neuropharmacology. 1988 Nov;27(11):1197-9
references.pmid: 3205387
references.citation: Arch Androl. 1997 Jul-Aug;39(1):79-83
references.pmid: 9202837
references.citation: Psychopharmacology (Berl). 1980;70(1):47-58
references.pmid: 6775334
references.citation: Can J Psychiatry. 2002 Feb;47(1):27-38
references.pmid: 11873706
references.citation: Brain Res Mol Brain Res. 1996 Sep 5;41(1-2):241-9
references.pmid: 8883957
references.citation: Pharmacol Biochem Behav. 1980 Nov;13(5):685-90
references.pmid: 7192405
references.citation: Behav Brain Res. 1989 Nov 1;35(2):95-109
references.pmid: 2818834
references.citation: Psychiatr Clin North Am. 1993 Dec;16(4):793-814
references.pmid: 8309813
references.citation: Cell Mol Neurobiol. 1996 Jun;16(3):325-44
references.pmid: 8818400