| Popis: |
The effect on rat catalepsy induced by Δ9-tetrahydrocannabinol (Δ9-THC) in association with haloperidol (HP) or clozapine (CLOZ) administration was investigated. Δ9-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 Δ9-THC+CLOZ administration. The CB1 antagonist SR141716A (0.5–5 mg kg−1, i.p.) reversed the increase mediated by Δ9-THC on HP-induced catalepsy. The D2 agonist quinpirole completely reversed the catalepsy induced by both HP and HP+Δ9-THC; however, higher doses of quinpirole were needed in the presence of Δ9-THC. The M1 antagonist scopolamine and α2 antagonist yohimbine were able to reduce the catalepsy induced by HP and HP+Δ9-THC in a similar manner. CLOZ and the 5-HT2A/2C antagonists ritanserin, RS102221 and SB242084 were more effective in antagonizing HP than HP+Δ9-THC-induced catalepsy. HP and CLOZ failed to inhibit in vitro [3H]CP-55,940 binding, while Δ9-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 Δ9-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. British Journal of Pharmacology (2003) 140, 520–526. doi:10.1038/sj.bjp.0705478 |
