EFFECTS OF CHRONIC METHAMPHETAMINE ON SCH23390-INDUCED OR HALOPERIDOL-INDUCED CATALEPSY, AND EFFECTS OF COADMINISTRATION OF SCH23390 OR HALOPERIDOL IN MICE

The influence of chronic treatment of mice with methamphetamine, an in direct dopamine agonist, on the cataleptic effects of ,-tetrahydro-3-m ethyl-5-phenyl-1H-3-benzazepin-7ol hydrochloride (SCH23390), a D-1 rec eptor agonist, or haloperidol, a mainly D-2 antagonist, was investigat ed. Once every other day treatment with 3 mg/kg SC methamphetamine for 15 days resulted in an increase in the catalepsy produced by haloperi dol(0.3 mg/kg IP) (haloperidol catalepsy), but in a decrease in the ca talepsy produced by SCH23390 (0.3 mg/kg IP) (SCH23390 catalepsy), 24 h and 7 days after withdrawal of methamphetamine. These effects of chro nic methamphetamine were antagonized by coadministration of either SCH 23390 (0.5 mg/kg SC) or haloperidol (1.0 mg/kg SC). These results sugg est that the decreased responsiveness to SCH23390 in chronic methamphe tamine-pretreated mice results from a supersensitivity of D-1 receptor s, and that the increased responsiveness to haloperidol catalepsy resu lts from a subsensitivity of D-2 receptors. The attenuated response to SCH23390 may be interpreted as an example of sensitization to methamp hetamine, and the enhanced haloperidol response as an example of toler ance to methamphetamine, based on the development of supersensitivity and subsensitivity of D-1 and D-2 receptors, respectively, after chron ic methamphetamine administration. Furthermore, it is suggested that c oadministration of either SCH23390 or haloperidol could prevent the de velopment of D-1 receptor supersensitivity and D-2 receptor subsensiti vity induced by chronic methamphetamine.