Modification of Catalepsy to Dopamine Antagonists after Chronic Cocaine or Cocaine plus Dopamine Antagonist Pretreatment in Mice

The influence of chronic pretreatment of mice with cocaine (indirect dopamine agonist), SCH23390 (dopamine D1 receptor antagonist), haloperidol (dopamine D2 receptor antagonist) or cocaine + dopamine antagonist on the cataleptic effects of SCH23390 and haloperidol was investigated. Challenge doses of haloperidol or SCH23390 given to mice I day and 7 days after chronic cocaine pretreatment (alternating days for 1 5 days) produced enhanced and attenuated cataleptic responses respectively, however, these responses were no longer produced when SCH23390 or haloperidol was given to mice pretreated chronically with a combination of cocaine and either SCH23390 or haloperidol. On the other hand, the pretreatment of SCH23390 (0.1-1.0 mg/kg s.c.) did not affect cataleptic responses induced by SCH23390 and haloperidol, whereas that of haloperidol (0.1-1.0 mg/kg s.c.) attenuated theｍ. The results suggest that the coadministration f SCH23390 with cocaine was able to block indirectly dopamine D2 receptor subsensitivity induced during the early withdrawal period (1-7 days) from chronic cocaine pretreatment, despite the fact that by itself SCH23390 did not have an effect on haloperidol catalepsy. Accordingly, the stimulatory effects of D2 receptors by a single administration of cocaine may be mediated mainly by an indirect stimulation of D2 receptor function secondary to its D1 stimulating action. Thus, coadministration of either SCHZ3390 or haloperidol with cocaine may prevent the development of D1 receptor supersensitivity and D2 receptor subsensitivity, respectively, induced during the early withdrawal period of chronic cocaine pretreatment.

コカイン

SCH23390

Haloperidol

カタレプシー反応

反復投与

マウス