The involvement of nicotinic receptor subtypes in the locomotor activity and analgesia induced by methamphetamine in mice.
We have previously reported that methamphetamine (METH) interacts with nicotinic acetylcholine receptor (nAChR) subtypes. This study investigated the involvement of nAChR in the effects of METH locomotion and pain. Chronic, but not acute, nicotine pretreatment potentiated METH-induced hyperlocomotion. This potentiation was abolished by pretreatment with methyllycaconitine, an antagonist of α-7nAChR, or dihydrobetaerythroidine, an antagonist of α-4/β-2nAChR. The mechanism by which amphetamines induce analgesia is not well understood. We investigated the analgesic effects of METH in the writhing, hot-plate and formalin tests and found that methyllycaconitine antagonized METH-induced analgesia in the writhing and formalin tests but not in the hot-plate test. Conversely, dihydrobetaerythroidine was only effective in the hot-plate test. We conclude that α-7nAChR activation by METH is involved in the analgesic effects induced by METH at both spinal and supraspinal levels, whereas METH activation of α-4/β-2nAChR is responsible for the analgesic effect elicited at the supraspinal level. These results show that nAChRs are involved in several actions of amphetamine derivatives and are an important target for the pharmacology of these drugs of abuse.
Camarasa
Jorge
J
Laboratory of Pharmacology and Pharmacognosy, Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. jcamarasa@ub.edu
Ratés
Sara García
SG
Pubill
David
D
Escubedo
Elena
E
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; C579166:Chrna7 protein, mouse; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D008694:Methamphetamine; D009538:Nicotine; D000157:Aconitine