Intense cocaine self-administration after episodic social defeat stress, but not after aggressive behavior: dissociation from corticosterone activation

Abstract

Rationale: An intense stress response characterizes both the dominant and submissive individuals during an aggressive confrontation, and these stress responses have enduring neural and behavioral consequences.

Objectives: In spite of similar glucocorticoid and corticolimbic dopamine activation, dominant and defeated individuals appear to diverge in terms of their drug taking. Do rats that are intermittently subjected to defeat stress become more sensitized to cocaine taking relative to rats that engage in aggressive bouts?

Methods: Separate groups of male Long-Evans rats were investigated after an initial 10-day period with four brief episodes of social defeat (intruders) or aggressive behavior (residents): (1) the corticosterone responses to the very first and the last confrontations were measured; (2) the locomotor response to an amphetamine (1 mg/kg) challenge 10 days after the last stress exposure served as an index of behavioral sensitization; (3) intravenous self-administration sessions assessed the reinforcing effects of 0.75 mg/kg/infusion cocaine when available after every fifth response (fixed ratio), when delivered after completing progressively more demanding response requirements (progressive ratio; 0.3 mg/kg/infusion), and when available during a 24-h binge of continuous access (0.3 mg/kg/infusion).

Results: Both social defeat of the intruder rat and attack behavior by the resident rat rapidly increased plasma levels of corticosterone after the first and last aggressive confrontation, indicating no habituation to these types of stress. Intermittent social defeat engenders a sensitized locomotor response to a 1 mg/kg amphetamine challenge and increases cocaine self-administration as indicated by more behavioral effort to obtain cocaine infusions and by accumulating more cocaine during 24 h of continuous access (binge). By contrast, experiences with aggressive behavior do not impact on the motorically activating and reinforcing effects of stimulant administrations.

Conclusions: The closely similar corticosterone activation in dominant and subordinate rats, followed by divergent patterns of cocaine self-administration indicates that different forms of social stress have dissociable effects on cocaine taking.