Haloperidol, but not clozapine, produces dramatic catalepsy in Δ9‐THC‐treated rats: possible clinical implications

摘要: 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 catalepsy, while no observed after CLOZ (1–20 s.c.) Δ9-THC+CLOZ administration. The CB1 antagonist SR141716A (0.5–5 i.p.) reversed the increase mediated Δ9-THC HP-induced catalepsy. The D2 agonist quinpirole completely both and HP+Δ9-THC; however, higher doses of were needed presence Δ9-THC. The M1 scopolamine α2 yohimbine able to reduce HP+Δ9-THC a similar manner. CLOZ 5-HT2A/2C antagonists ritanserin, RS102221 SB242084 more effective antagonizing than HP+Δ9-THC-induced catalepsy. HP failed inhibit vitro [3H]CP-55,940 binding, did not show an appreciable affinity for receptor. It suggested that different effects following may depend receptor-binding profiles two antipsychotics. The preferential use rather treatment psychotic symptoms cannabis abusers discussed. Keywords: Antipsychotic, bar test, extrapyramidal symptoms, serotonin Introduction Considerable research has indicated precipitate psychosis-like among vulnerable individuals. Moreover, it been shown increases risk relapse, as well worsens prolongs patients who have already developed disorder (for review, see Degenhardt & Hall, 2002). Antipsychotic drugs are largely employed management schizophrenia other disorders; possible interaction between antipsychotic adequately investigated. Depending their pharmacological properties, antipsychotics currently used clinical practice divided into conventional antipsychotics, such (HP), atypical (CLOZ). improvements treated often accompanied appearance side (EPS), akinesia, rigidity tremors. blockade dopamine receptor basal ganglia associated development EPS (Kapur Remington, 2001). Atypical able, grades, antagonize striatal at therapeutic doses; they low propensity induce (Tarsi et al., 2002). which author is being read, this peculiarity favorable D2/M1 (Haraguchi 1997), D2/5-HT2A/2C (Meltzer 1989; Reavill 1999), D2/α2 antagonism ratio (Kalkman 1998). It was, indeed, hypothesized profile might counteract ganglia, leading reduced incidence EPS. Like blockade, cannabinoid stimulation known affect motor activity. Consistently, several researches involving volunteers given agonists laboratory showed impairment variety tasks (Yesavage 1985; Wilson 1994). In rats, dose-dependent ataxia systemic cannabinoids (Chaperon Thiebot, 1999). Furthermore, microinjected striatum produced immobility (Gough Olley, 1978). Within central nervous system, receptors densely expressed (Herkenham 1991), colocalization (Hermann previous study, Anderson al. (1996) CP-55,940 exacerbated raclopride. aim present study determine (Δ9-THC), most psychoactive component marijuana.