High affinity α3β4 nicotinic acetylcholine receptor ligands AT-1001 and AT-1012 attenuate cocaine-induced conditioned place preference and behavioral sensitization in mice

摘要: Cholinergic signaling via the nicotinic acetylcholine receptors (nAChRs) in mesolimbic circuitry is involved rewarding effects of abused drugs such as cocaine and opioids. In mouse studies, nonselective nAChR antagonist mecamylamine blocks cocaine-induced conditioned place preference (CPP) behavioral sensitization. Among subtype-selective antagonists, β2-selective dihydrobetaerythroidine α7 methyllycaconitine (MLA), but not MLA alone prevent sensitization to cocaine. Since role α3β4 subtype unknown, present study investigated effect two potent selective ligands, AT-1001 AT-1012, on acquisition CPP mice. At 5-30mg/kg, produced robust CPP, whereas locomotor activity was only observed at higher doses (20-30mg/kg). Pretreatment with (1-10mg/kg) or AT-1012 (3-10mg/kg) blocked induced by 5mg/kg cocaine, 30mg/kg Lower (0.3-1mg/kg) (1-3mg/kg) did affect increase 5 But AT-1001, these doses, These results indicate that play a ligands can attenuate phenomena. functional has also been shown block nicotine self-administration rats, suggest nAChRs may be target for treatment addiction well cocaine-nicotine comorbid addiction.