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

Abstract

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 [18F]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.

Fig. 1

D2 receptor availability ([¹⁸F]FCP DVR) in the caudate nucleus and putamen in five dominant (D) and seven subordinate (S) monkeys. Letters indicate individual monkeys (see Table 1). Horizontal line indicates the mean [¹⁸F]FCP DVR. *p<0.05

Fig. 2

Latency in seconds to touch a novel object in five dominant (DOM), seven subordinate (SUB), and nine individually housed (IND) monkeys. Letters indicate individual monkeys (see Table 1), *p<0.05

Fig. 3

Relationship between D2 receptor availability ([¹⁸F]FCP DVR) in the caudate nucleus or putamen and reaction to novelty (latency in seconds to touch a novel object) in socially housed monkeys