Haloperidol, but not clozapine, produces dramatic catalepsy in Δ 9-THC-treated rats: Possible clinical implications

1. The effect on rat catalepsy induced by Δ 9- tetrahydrocannabinol (Δ 9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. 2. Δ 9-THC dose-dependently increased HP (0.05 -1 mg kg -1, s.c.)-induced rat catalepsy, while no catalepsy was observed after CLOZ (1-20mg kg -1, s.c.) or Δ 9-THC + CLOZ administration. 3. The CB 1 antagonist SR141716A (0.5-5 mg kg -1, i.p.) reversed the increase mediated by Δ 9-THC on HP-induced catalepsy. 4. The D 2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP + Δ 9-THC; however, higher doses of quinpirole were needed in the presence of Δ 9-THC. 5. The M 1 antagonist scopolamine and α 2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP + Δ 9-THC in a similar manner. 6. CLOZ and the 5-HT 2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP + Δ 9-THC-induced catalepsy. 7. HP and CLOZ failed to inhibit in vitro [ 3H]CP-55,940 binding, while Δ 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 Δ 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.