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 alpha-7nAChR, or dihydrobetaerythroidine, an antagonist of alpha-4/beta-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 a-7nAChR activation by METH is involved in the analgesic effects induced by METH at both spinal and supraspinal levels, whereas METH activation of alpha-4/beta-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. Behavioural Pharmacology 20:623-630 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.