Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum

Abstract

Rationale: Studies in human and non-human primates demonstrate that social status is an important determinant of cocaine reinforcement. However, it is unclear whether social rank is associated with other traits that also predispose to addiction and whether social status similarly predicts cocaine self-administration in rats.

Objectives: The objective of this study is to investigate whether social ranking assessed using a resource competition task affects (i) the acquisition, maintenance and reinstatement of cocaine self-administration; (ii) the dopaminergic markers in the striatum; and (iii) the expression of ancillary traits for addiction.

Methods: Social ranking was determined in group-housed rats based upon drinking times during competition for a highly palatable liquid. Rats were then evaluated for cocaine self-administration and cue-induced drug reinstatement or individual levels of impulsivity, anxiety and novelty-induced locomotor activity. Finally, dopamine content, dopamine transporter (DAT) and dopamine D2/D3 (D2/3) receptor binding were measured postmortem in the dorsal and ventral striatum.

Results: Rats deemed socially dominant showed enhanced novelty reactivity but were neither more impulsive nor anxious compared with subordinate rats. Dominant rats additionally maintained higher rates of cocaine self-administration but showed no differences in the acquisition, extinction and reinstatement of this behaviour. D2/3 binding was elevated in the nucleus accumbens shell and dorsal striatum of dominant rats when compared to subordinate rats, and was accompanied by elevated DAT and reduced dopamine content in the nucleus accumbens shell.

Conclusions: These findings show that social hierarchy influences the rate of self-administered cocaine but not anxiety or impulsivity in rats. Similar to non-human primates, these effects may be mediated by striatal dopaminergic systems.

Keywords: Anxiety; High responder; Impulsivity; Psychostimulants; Resource competition; Social status.

Fig. 1

a Study design. b Drinking times of socially dominant and subordinate rats across the last 3 days of competition *p < 0.05 main effect of rank. c Drinking times before, during and after the resource competition task. d Tube test performance and e frequency distribution of the total number of wins in socially dominant and subordinate rats, *p < 0.05

Fig. 2

a Acquisition of cocaine self-administration *p < 0.05 main effect lever, +p < 0.05 lever × day interaction. b Extinction and cue-induced reinstatement *p < 0.05 main effect of day. c Active lever and d inactive lever responses during dose response testing. *p < 0.05 main effect of rank, #p < 0.05 main effect of dose, in socially dominant and subordinate rats

Fig. 3

a Novelty-induced locomotor activity *p < 0.05 main effect of rank, #p < 0.05 main effect of day. b Light/dark box performance *p < 0.05 main effect of side and c premature responding d accuracy and e omissions on the five-choice serial-reaction time task in socially dominant and subordinate rats

Fig. 4

Quantitative assessment of D_2/3 receptors, DAT and DA content in the dorsal and ventral striatum of socially dominant and subordinate rats, *p < 0.05 main effect of rank