title: Effects of blockade of α4β2 and α7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats.
abstract: Exposure to environmental stimuli conditioned to nicotine consumption critically contributes to the high relapse rates of tobacco smoking. Our previous work demonstrated that non-selective blockade of nicotinic acetylcholine receptors (nAChRs) reversed the cue-induced reinstatement of nicotine seeking, indicating a role for cholinergic neurotransmission in the mediation of the conditioned incentive properties of nicotine cues. The present study further examined the relative roles of the two major nAChR subtypes, α4β2 and α7, in the cue-induced reinstatement of nicotine seeking. Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, free base) on a fixed-ratio 5 schedule of reinforcement. A nicotine-conditioned cue was established by associating a sensory stimulus with each nicotine infusion. After nicotine-maintained responding was extinguished by withholding the nicotine infusion and its paired cue, reinstatement test sessions were conducted with re-presentation of the cue but without the availability of nicotine. Thirty minutes before the tests, the rats were administered the α4β2-selective antagonist dihydro-β-erythroidine (DHβE) and α7-selective antagonist methyllycaconitine (MLA). Pretreatment with MLA, but not DHβE, significantly reduced the magnitude of the cue-induced reinstatement of responses on the active, previously nicotine-reinforced lever. In different sets of rats, MLA altered neither nicotine self-administration nor cue-induced reinstatement of food seeking. These results demonstrate that activation of α7 nAChRs participates in the mediation of the conditioned incentive properties of nicotine cues and suggest that α7 nAChRs may be a promising target for the development of medications for the prevention of cue-induced smoking relapse.
authors: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors: Xiu
authors: X
authors: Liu
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005502:Food; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012055:Reinforcement Schedule; D012646:Self Administration; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors*
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; C054634:methyllycaconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000157:Aconitine
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