Activational Effects of Social Stress on IV Cocaine Self-administration in Rats

The objective of the current studies was to investigate how social stress modulates IV cocaine self-administration. Specifically, an experimental protocol was developed in rats that assessed the impact of recurrent non-injurious social confrontations with an aggressive opponent on subsequent rate of cocaine self-administration behavior, maintained across a range of doses. Initially, the cocaine dose-effect function for intravenous self-administration was determined, reinforcing every fifth lever press (fixed ratio or FR 5), with each dose (0.031, 0.063, 0.125, 0.25 mg/infusion and saline) being assessed for at least 3 days. Subsequently, the rats were assigned to two groups, one group being exposed as intruders to the threats of an aggressive resident rat for 60 min, while being protected by a screen, immediately before a session for IV self-administration with maximally 15 cocaine infusions. A second group served as control, being determined for a second cocaine dose-effect function without any social stress exposure. Additional rats performed conditioned lever pressing that was reinforced by food at a rate and pattern closely similar to that characteristic for cocaine IV self-administration (joint FI 3 min FR 5). Recurrent episodes of mild social stress increased the rate of responding on the cocaine-reinforced lever. This increase is seen after rats have been exposed to the threats of an aggressive opponent, but not after social or single housing. These behaviorally activating effects of social stress (1) are long-lasting, (2) are not subject to habituation, (3) are selective to responding that is reinforced by IV cocaine, do not extend to non-reinforced lever pressing, or to food-reinforced lever pressing, (4) are most prominent in the time-out period during and after the cocaine infusion, (5) do not shorten the intervals between consecutive cocaine infusions, and (6) are most evident at lower to intermediate cocaine doses. These results suggest that social stress effectively activates the motor routines that are involved in cocaine-seeking rather than increasing the drug's reinforcing efficacy.