Effects of osemozotan, ritanserin and azasetron on cocaine-induced behavioral sensitization in mice.
Repeated intermittent administration of psychostimulants causes behavioral sensitization in rodents. Previous studies using serotonin (5-HT) receptor ligands show that the 5-HT system is involved in cocaine-induced behavioral sensitization in rats, but the role of the 5-HT system has not been studied in mice. The present study examined the effects of the 5-HT(1A) receptor agonist osemozotan, the 5-HT(2) receptor antagonist ritanserin and the 5-HT(3) receptor antagonist azasetron on cocaine-induced behavioral sensitization in male ddY mice. Repeated administration of cocaine for 7 days enhanced cocaine-induced locomotor activity, and this sensitization was observed even after withdrawal for 7-14 days. Cocaine-induced behavioral sensitization after a 7-day withdrawal was significantly reduced with the coadministration of osemozotan, ritanserin or azasetron with cocaine repeatedly for 7 days. A single injection of osemozotan or ritanserin before cocaine challenge also reduced repeated cocaine-induced behavioral sensitization. However, none of these ligands inhibited cocaine-induced behavioral sensitization, when each drug was administered for 7 days after repeated cocaine administration. These results suggest that the central 5-HT system plays a role in the development and expression, but not maintenance, of behavioral sensitization in cocaine-treated mice.
Ago
Yukio
Y
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, Japan.
Nakamura
Shigeo
S
Hayashi
Aiko
A
Itoh
Soichi
S
Baba
Akemichi
A
Matsuda
Toshio
T
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010078:Oxazines / Q000494:pharmacology*; D016713:Ritanserin / Q000494:pharmacology*
D014150:Antipsychotic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D004149:Dioxoles; D010078:Oxazines; D016713:Ritanserin; C070671:azasetron; D003042:Cocaine; C096294:osemozotan