Effects of alpha4beta2 and alpha7 nicotinic acetylcholine receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats

Abstract

Acute dependence can be observed when naloxone is administered 24 h after even a single dose of morphine, and nicotine attenuates this naloxone-precipitated withdrawal syndrome. This acute dependence has been hypothesized to be associated with a dopaminergic mechanism. In the present study, the role of nicotinic acetylcholine receptor subtypes in the place aversion induced by naloxone in single-dose morphine-treated rats was investigated. Methyllycaconitine (1, 2 and 5 mg/kg), an alpha7 nicotinic acetylcholine receptor subtype inhibitor, significantly and dose dependently inhibited the attenuating effect of nicotine on naloxone-induced place aversion. In contrast, dihydroxy-beta-erithroidine (1, 2 and 5 mg/kg), an alpha4beta2 nicotinic acetylcholine receptor subtype inhibitor, did not have any effect on the attenuating effect of nicotine on naloxone-induced place aversion. These findings suggested that the alpha7 nicotinic acetylcholine receptor subtype is associated with the place aversion induced by naloxone in single-dose morphine-treated rats. Nicotinic acetylcholine receptor subtype inhibitors warrant further study as possible treatment for acute dependence.