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

Psychopharmacology (Berl). 2016 May;233(10):1829-35. doi: 10.1007/s00213-016-4250-9. Epub 2016 Feb 25.


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: 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.

Methods: 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 10 μg/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 α4β2* nAChRs were measured 4 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.

Keywords: In vivo binding; Nicotine self-administration; Non-human primates; Positron emission tomography.

MeSH terms

  • Animals
  • Azetidines / analysis
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / metabolism
  • Fluorine Radioisotopes / analysis
  • Male
  • Nicotine / administration & dosage*
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / analysis
  • Receptors, Nicotinic / analysis
  • Receptors, Nicotinic / biosynthesis*
  • Self Administration


  • A 85380
  • Azetidines
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Nicotinic
  • nicotinic receptor alpha4beta2
  • Nicotine