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

Abstract

RATIONALE 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. OBJECTIVES Determine if short access to nicotine in a non-human primate model of nicotine self-administration is sufficient to induce nAChRs upregulation. METHODS We combined a nicotine self-administration paradigm with in vivo measure of α4β2* nAChRs using 2-[18F]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 μg/kg per injection). Monkeys were trained to self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Intermittent access (one hour daily per weekday) to nicotine was allowed for four weeks and levels of α4β2* nAChRs were measured four days later. RESULTS 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). CONCLUSIONS These results indicate that intermittent nicotine exposure is sufficient to produce change in nAChRs expression.

Acute Ethanol Administration Upregulates Synaptic α4-Subunit of Neuronal Nicotinic Acetylcholine Receptors within the Nucleus Accumbens and Amygdala

“…Here we describe these tiers of selectivity. At the level of brain regions, nicotine upregulates nAChRs in hippocampus, cortex, amygdala ( Le Foll et al, 2016 ) and midbrain; but not in the thalamus. Among cell types within brain regions, nicotine upregulates nAChRs strongly in the somata of VTA GABAergic neurons, but only modestly in the somata of VTA dopaminergic neurons.…”

Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula

“…This is an important distinction, as non-contingent versus contingent nicotine exposure can lead to different plasticity changes ( Caillé et al, 2009 ; Metaxas et al, 2010 ). Studies that have documented nAChR upregulation in nicotine SA models ( Donny et al, 2000 ; Le Foll et al, 2016 ) have relied on methods (e.g., radioligand binding, quantitative immunohistochemistry, etc.) that are unable to examine nAChR functional activity.…”

Effects of galantamine on smoking behavior and cognitive performance in treatment‐seeking smokers prior to a quit attempt

“…Galantamine also directly stimulates α7 and α4β2 nicotinic acetylcholine receptors (nAChRs) via its positive allosteric modulator actions (Samochocki et al, 2003). Because nAChRs represent an important treatment target for TUD (Le Foll et al, 2016), further examination of galantamine’s efficacy as a treatment for TUD is warranted.…”