Haloperidol, but not clozapine, produces dramatic catalepsy in Δ9THC-treated rats:: possible clinical implications

1 The effect on rat catalepsy induced by Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. 2 Delta(9)-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 Delta(9)-THC + CLOZ administration. 3 The CB1 antagonist SR141716A (0.5-5 mg kg(-1), i.p.) reversed the increase mediated by Delta(9)-THC on HP-induced catalepsy. 4 The D-2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP + Delta(9)-THC; however, higher doses of quinpirole were needed in the presence of Delta(9)-THC. 5 The M-1 antagonist scopolamine and alpha(2) antagonist yohimbine were able to reduce the catalepsy induced by HP and HP + Delta(9)-THC in a similar manner. 6 CLOZ and the 5-HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP + Delta(9)-THC-induced catalepsy. 7 HP and CLOZ failed to inhibit in vitro [H-3]CP-55,940 binding, while Delta(9)-THC and SR141716A did not show an appreciable affinity for the D-2 receptor. 8 It was suggested that the different effects on rat catalepsy induced by Delta(9)-THC following HP or CLOZ administration may depend on the receptor-binding profiles of the two antipsychotics. 9 The preferential use of CLOZ rather than HP in the treatment of psychotic symptoms in cannabis abusers was discussed.