The effect on rat
catalepsy induced by Delta9-tetrahydrocannabinol (Delta9-THC) in association with
haloperidol (HP) or
clozapine (CLOZ) administration was investigated. Delta9-THC dose-dependently increased HP (0.05-1 mg kg-1, s.c.)-induced rat
catalepsy, while no
catalepsy was observed after CLOZ (1-20 mg kg-1, s.c.) or Delta9-THC+CLOZ administration. The CB1 antagonist
SR141716A (0.5-5 mg kg-1, i.p.) reversed the increase mediated by Delta9-THC on HP-induced
catalepsy. The D2 agonist
quinpirole completely reversed the
catalepsy induced by both HP and HP+Delta9-
THC; however, higher doses of
quinpirole were needed in the presence of Delta9-THC. The M1 antagonist
scopolamine and alpha2 antagonist
yohimbine were able to reduce the
catalepsy induced by HP and HP+Delta9-
THC in a similar manner. CLOZ and the 5-HT2A/2C antagonists
ritanserin, RS102221 and
SB242084 were more effective in antagonizing HP than HP+Delta9-
THC-induced
catalepsy.7 HP and CLOZ failed to inhibit in vitro [3H]CP-55,940 binding, while Delta9-THC and
SR141716A did not show an appreciable affinity for the D2 receptor. It was suggested that the different effects on rat
catalepsy induced by Delta9-THC following HP or CLOZ administration may depend on the receptor-binding profiles of the two
antipsychotics. The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed.