Bernard Le Foll1,2,3,4, Svetlana I Chefer5,6, Alane S Kimes5,7, Elliot A Stein5, Steven R Goldberg8, Alexey G Mukhin5,9. 1. Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, ON, Canada, M5S 2S1. bernard.lefoll@camh.ca. 2. Departments of Family and Community Medicine, Pharmacology, Psychiatry, Institute of Medical Sciences, University of Toronto, Toronto, Canada. bernard.lefoll@camh.ca. 3. Ambulatory Care and Structured Treatment Program, Centre for Addiction and Mental Health, Toronto, Canada. bernard.lefoll@camh.ca. 4. Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA. bernard.lefoll@camh.ca. 5. Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA. 6. The Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Disease, NIH, Fort.Detrick, Frederick, MD, 21702, USA. 7. Office of the Clinical Director (retired), Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA. 8. Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, 21224, USA. 9. Department Psychiatry and Behavioral Sciences and Center for Smoking Cessation, Duke University Medical Center, 2424 Erwin Road, Suite 201, Durham, NC, 27705, USA.
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: 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.
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.
Entities:
Keywords:
In vivo binding; Nicotine self-administration; Non-human primates; Positron emission tomography
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