Journal Article

Impact of short access nicotine self-administration on expression of alpha 4 beta 2 nicotinic acetylcholine receptors in non-human primates

Le Foll, Bernard, Chefer, Svetlana I, Mukhin, Alexey G, Goldberg, Steven R, Kimes, Alane S, Stein, Elliot A

2016

Overview

Although nicotine exposure upregulates the alpha 4 beta 2* subtype of nicotinic acetylcholine receptors (nAChRs), the upregulation of nAChRs in non-human primates voluntarily self-administering nicotine has never been demonstrated. The objective of the study is to determine if short access to nicotine in a non-human primate model of nicotine self-administration is sufficient to induce nAChRs upregulation. We combined a nicotine self-administration paradigm with in vivo measure of alpha 4 beta 2* nAChRs using 2-[ super(18)F]fluoro-A-85380 (2-FA) and positron emission tomography (PET) in six squirrel monkeys. PET measurement was performed before and after intravenous nicotine self-administration (unit dose 10 mu g/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (1 h daily per weekday) to nicotine was allowed for 4 weeks and levels of alpha 4 beta 2* nAChRs were measured 4 days later. This intermittent access was sufficient to induce upregulation of alpha 4 beta 2* receptors in the whole brain (31 % upregulation) and in specific brain areas (+36 % in amygdala and +62 % in putamen). These results indicate that intermittent nicotine exposure is sufficient to produce change in nAChRs expression.

• Subject: Saimiri