Not all stress is equal: CREB is not necessary for restraint stress reinstatement of cocaine-conditioned reward.

Stress elicits relapse to cocaine seeking in humans and in animal models. Cyclic AMP response element binding protein (CREB) is required for swim stress-induced reinstatement of cocaine conditioned place preference. However, the role of CREB in other stress-induced reinstatement models has not been examined. To determine whether CREB is required across different stressors we examined the ability of restraint to elicit reinstatement of cocaine-conditioned place preference in wild-type and CREBαΔ mutant mice. In contrast to previously published differences in swim stress-induced reinstatement, both wild-type and CREBαΔ mutant mice demonstrated restraint stress elicited reinstatement of cocaine-conditioned reward. While CREB is necessary for swim stress-elicited zif268 expression within the nucleus accubmens (NAc) shell and prelimbic cortex (PrL), restraint-stress-elicited comparable increases in zif268 expression within these regions in both wild-type and CREBαΔ mutant mice. Our findings suggest that not all stressors engage the same circuits or molecular mechanisms to elicit reinstatement behavior.