Effects of social reorganization on dopamine D2/D3 receptor availability and cocaine self-administration in male cynomolgus monkeys

Psychopharmacology (Berl). 2017 Sep;234(18):2673-2682. doi: 10.1007/s00213-017-4658-x. Epub 2017 Jun 12.

Abstract

Rationale: Studies have demonstrated that brain dopamine D2/D3 receptors (D2/D3R) and the reinforcing effects of cocaine can be influenced by a monkey's position in the social dominance hierarchy.

Objective: In this study, we manipulated the social ranks of monkeys by reorganizing social groups and assessed effects on D2/D3R availability and cocaine self-administration.

Methods: Male cynomolgus monkeys (N = 12) had been trained to self-administer cocaine under a concurrent cocaine-food reinforcement schedule. Previously, PET measures of D2/D3R availability in the caudate nucleus and putamen had been obtained with [18F]fluoroclebopride during cocaine abstinence, while monkeys lived in stable social groups of four monkeys/pen. For this study, monkeys were reorganized into groups that consisted of (1) four previously dominant, (2) four previously subordinate, and (3) a mix of previously dominant and subordinate monkeys. After 3 months, D2/D3R availability was redetermined and cocaine self-administration was reexamined.

Results: D2/D3R availability significantly increased after reorganization in monkeys who were formerly subordinate, with the greatest increases observed in those that became dominant. No consistent changes in D2/D3R availability were observed in formerly dominant monkeys. Cocaine self-administration did not vary according to rank after reorganization of social groups. However, when compared to their previous cocaine self-administration data, the potency of cocaine as a reinforcer decreased in 9 of 11 monkeys.

Conclusions: These results indicate that changing the social conditions can alter D2/D3R availability in subordinate monkeys in a manner suggestive of environmental enrichment. In most monkeys, social reorganization shifted the cocaine dose-response curve to the right, also consistent with environmental enrichment.

Keywords: Cynomolgus monkey; Dopamine receptors; Drug choice; Drug self-administration; PET imaging; Social rank.

MeSH terms

  • Animals
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Cocaine / administration & dosage*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Hierarchy, Social*
  • Macaca fascicularis
  • Male
  • Putamen / diagnostic imaging
  • Putamen / drug effects
  • Putamen / metabolism
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Reinforcement, Psychology
  • Self Administration
  • Social Dominance*

Substances

  • Dopamine Uptake Inhibitors
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Cocaine