Blocking α4β2 and α7 nicotinic acetylcholine receptors inhibits the reinstatement of morphine-induced CPP by drug priming in mice

Investigating the interaction between nicotinic and opioid receptors is of great interest for both basic mechanistic and clinical reasons. Morphine and nicotine, two common drugs of abuse, share several behavioral and rewarding properties. However, little is known about the subtypes of nicotinic acetylcholine receptors (nAChR) in the reinstatement of morphine-induced conditioned place preference (CPP). In this study, we found that a non-specific nAChR agonist, nicotine (0.5 mg/kg), had no effects on the reinstatement of morphine-induced CPP. However, we found that pretreatment with specific α4β2 and α7 nAChR subtype antagonists, dihydroxy-β-erithroidine (DHβE, 5 mg/kg) and methyllycaconitine (MLA, 4 mg/kg), 20 min prior to administration of morphine, inhibited the reinstatement of morphine-induced CPP by drug priming in mice. Furthermore, depression of the reinstatement of morphine-induced CPP by a single DHβE or MLA treatment lasted at least three days later when the reinstatement was induced by morphine priming. The data suggest that specific nAChR subtypes, i.e., α4β2 and α7, may contribute to the reinstatement of morphine-induced CPP by drug priming in mice.

Research highlights
► Pretreatment with α4β2 nAChR antagonist inhibited the reinstatement of morphine.
► Pretreatment with α7 nAChR antagonists inhibited the reinstatement of morphine.
► α4β2 and α7 nAChR subtypes may contribute to the reinstatement of morphine.