Haloperidol, but not clozapine, produces dramatic catalepsy in delta9-THC-treated rats: possible clinical implications.
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.
Marchese
Giorgio
G
Neuroscienze S.c.a r.l., Cagliari 09123, Italy.
Casti
Paola
P
Ruiu
Stefania
S
Saba
PierLuigi
P
Sanna
Angela
A
Casu
GianLuca
G
Pani
Luca
L
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D003024:Clozapine / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000378:metabolism / Q000633:toxicity*; D004357:Drug Synergism; D006220:Haloperidol / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D013759:Dronabinol; D003024:Clozapine; D006220:Haloperidol