Differences in D2 dopamine receptor availability and reaction to novelty in socially housed male monkeys during abstinence from cocaine

• Published in: Psychopharmacologia 2010-03, Vol.208 (4), p.585-592
• Main Authors: Czoty, Paul W., Gage, H. Donald, Nader, Michael A.
• Format: Article
• Language: English
• Subjects: Animal behavior; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Caudate Nucleus - diagnostic imaging; Caudate Nucleus - metabolism; Cocaine; Cocaine - administration & dosage; Cocaine - pharmacology; Cocaine-Related Disorders - diagnostic imaging; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - psychology; Cynomolgus; Disease Models, Animal; Exploratory Behavior - drug effects; Fluorine Radioisotopes; Hierarchy, Social; Housing, Animal; Macaca fascicularis; Male; Medical sciences; Monkeys & apes; Neuropharmacology; Neurosciences; Neurotransmitters; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Positron-Emission Tomography - methods; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Putamen - diagnostic imaging; Putamen - metabolism; Radioligand Assay - methods; Receptors, Dopamine D2 - metabolism; Self Administration
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1756-4

Rationale Studies in socially housed monkeys have demonstrated an influence of position in the social dominance hierarchy on brain dopamine D2 receptors and the reinforcing effects of cocaine that dissipates after long-term cocaine self-administration. Objective The aims of the study were to examine the effects of abstinence from cocaine on D2 receptors in socially housed monkeys and to extend behavioral characterizations to measures of reactivity to a novel object. Materials and methods Twelve socially housed male cynomolgus monkeys with extensive cocaine self-administration experience were used (average lifetime intakes ∼270 and 215 mg/kg for dominant and subordinate monkeys, respectively). Abstinence lasted for approximately 8 months, after which D2 receptor availability was assessed using positron emission tomography and the D2 ligand [ 18 F]fluoroclebopride. Reaction to novelty was also assessed in these subjects as well as nine individually housed monkeys. Results During abstinence, D2 receptor availability in the caudate nucleus was significantly higher in dominant versus subordinate monkeys. Average latency to touch a novel object was also significantly higher in dominant monkeys compared to subordinates or individually housed monkeys. In socially experienced monkeys, a significant positive correlation was observed between caudate nucleus D2 receptor availability and latencies to touch the novel object. Conclusions Although chronic cocaine self-administration blunts the ability of social dominance to alter D2 receptor availability and sensitivity to the reinforcing effects of cocaine, this influence reemerges during abstinence. In addition, the data suggest that prior experience with social dominance can lead to longer latencies in reaction to novelty—a personality trait associated with low vulnerability to cocaine abuse.