title: Delta9-Tetrahydrocannabinol-induced cognitive deficits are reversed by olanzapine but not haloperidol in rats.
abstract: Cannabis is the most widely used illicit substance. Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive impairment that closely resembles the impairment observed in schizophrenic patients. THC has also been known to impair spatial memory in rats tested in the eight-arm radial maze. We previously reported that microinjection of THC (20 microg/side) into the rat dorsal hippocampus impaired spatial memory and that i.p. injection of THC (6 mg/kg) decreased the extracellular levels of acetylcholine (ACh) in the dorsal hippocampus. In the present study, we compared the effects of olanzapine, an atypical antipsychotic, with those of haloperidol, a typical neuroleptic, on the impairments of spatial memory and decreased ACh levels induced by THC (6 mg/kg, i.p.) in rats. We found that olanzapine (0.1 mg/kg, i.p.) reversed the THC-induced memory deficits and decrease in extracellular ACh levels, whereas haloperidol (0.03-0.3 mg, i.p.) had no effect. These results suggest that olanzapine may improve the THC-induced impairment of spatial memory, partly by enhancing ACh release in the dorsal hippocampus. Therefore, olanzapine could attenuate the acute short-term and working memory deficits induced by cannabis.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Fukuoka 814-0180, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishigami
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000209:etiology / Q000517:prevention & control*; D013759:Dronabinol / Q000009:adverse effects*; D005110:Extracellular Space / Q000378:metabolism; D006213:Hallucinogens / Q000009:adverse effects*; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000150:complications; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control; D017551:Microdialysis; D000077152:Olanzapine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D006213:Hallucinogens; D001569:Benzodiazepines; D013759:Dronabinol; D006220:Haloperidol; D000077152:Olanzapine; D000109:Acetylcholine