Effects of quetiapine on phencyclidine-induced cognitive deficits in mice: a possible role of alpha1-adrenoceptors.
Accumulating evidence suggests that alpha(1)-adrenoceptors may be involved in the mechanisms of action of some antipsychotic drugs. The present study was undertaken to examine the effects of quetiapine, an atypical antipsychotic drug with alpha(1)-adrenoceptor antagonism, on cognitive deficits in mice after repeated administration of the NMDA receptor antagonist phencyclidine (PCP). Subsequent subchronic (14 days) administration of quetiapine (1.0, 10, or 30 mg/kg, p.o.) attenuated PCP (10 mg/kg/day for 10 days)-induced cognitive deficits in mice, in a dose dependent manner. Furthermore, PCP (10 mg/kg)-induced cognitive deficits were also significantly ameliorated by subsequent subchronic (14 days) administration of the selective alpha(1)-adrenoceptor antagonist prazosin (1.0 mg/kg/day, p.o.). Moreover, Western blot analysis revealed that levels of two subtypes (alpha(1A) and alpha(1B)) of alpha(1)-adrenoceptors were significantly lower in the brains of PCP-treated mice than in those of saline-treated mice. These findings suggest that repeated PCP administration could decrease the density of alpha(1)-adrenoceptors in mouse brain, and that subsequent subchronic administration of quetiapine might ameliorate PCP-induced cognitive deficits via alpha(1)-adrenoceptors. Therefore, it is likely that antagonism at alpha(1)-adrenoceptors is involved in the mechanism underlying quetiapine's psychopharmacological action.
Tanibuchi
Yuko
Y
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba 260-8670, Japan.
Fujita
Yuko
Y
Kohno
Mami
M
Ishima
Tamaki
T
Takatsu
Yuto
Y
Iyo
Masaomi
M
Hashimoto
Kenji
K
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D003987:Dibenzothiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010622:Phencyclidine; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018340:Receptors, Adrenergic, alpha-1; D000069348:Quetiapine Fumarate; D010622:Phencyclidine; D011224:Prazosin