Impact of short access nicotine self-administration on expression of α4β2* nicotinic acetylcholine receptors in non-human primates.

Abstract

Although nicotine exposure upregulates the α4β2* 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 α4β2* nAChRs using 2-[(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 10μg/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (1h daily per weekday) to nicotine was allowed for 4weeks and levels of α4β2* nAChRs were measured 4days later. This intermittent access was sufficient to induce upregulation of α4β2* 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.