Suppression of methamphetamine-seeking behavior by nicotinic agonists.
To understand the mechanism of methamphetamine (MAP) craving from the viewpoint of nicotinic acetylcholinergic transmission, we examined the responsible site of the brain for anticraving effects produced by nicotinic agonists by using a MAP self-administration paradigm in rats. Systemic nicotine and an acetylcholinesterase inhibitor, donepezil, attenuated the reinstatement of MAP-seeking behavior by means of the activation of nicotinic acetylcholinergic receptors, but not muscarinic acetylcholinergic receptors, in the nucleus accumbens core, prelimbic cortex, amygdala, and hippocampus. Among these regions, with the exception of the hippocampus, we also found functional differences in this reinstatement. The nicotinic antagonist mecamylamine alone did not reinstate MAP-seeking behavior. These results suggest that the inactivation of nicotinic acetylcholinergic transmission may be an essential factor in the appearance of MAP-seeking behavior, and, thus, the normalization of the inactivated state may result in the suppression of the reinstatement. Our findings also indicate that there are functional differences in the responsible brain subregions. Extending this view to the treatment of MAP dependence, our results suggest that activators of nicotinic acetylcholinergic transmission are possible anticraving agents.
Hiranita
Takato
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nawata
Yoko
Y
Sakimura
Katsuya
K
Anggadiredja
Kusnandar
K
Yamamoto
Tsuneyuki
T
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D008694:Methamphetamine / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D007189:Indans; D018722:Nicotinic Agonists; D010880:Piperidines; D011978:Receptors, Nicotinic; D008694:Methamphetamine; D008464:Mecamylamine; D009538:Nicotine; D000077265:Donepezil; D008012:Lidocaine; D012601:Scopolamine; D000110:Acetylcholinesterase