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Haloperidol, but not clozapine, produces dramatic catalepsy in delta9-THC-treated rats: possible clinical implications.

Abstract
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.
AuthorsGiorgio Marchese, Paola Casti, Stefania Ruiu, PierLuigi Saba, Angela Sanna, GianLuca Casu, Luca Pani
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 140 Issue 3 Pg. 520-6 (Oct 2003) ISSN: 0007-1188 [Print] England
PMID12970091 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Dronabinol
  • Clozapine
  • Haloperidol
Topics
  • Animals
  • Catalepsy (chemically induced, metabolism, physiopathology)
  • Clozapine (metabolism, therapeutic use, toxicity)
  • Dose-Response Relationship, Drug
  • Dronabinol (metabolism, toxicity)
  • Drug Synergism
  • Haloperidol (metabolism, therapeutic use, toxicity)
  • Male
  • Protein Binding (physiology)
  • Rats
  • Rats, Sprague-Dawley

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