The HP circuit is important in regulating nicotine dependence and withdrawal and is more generally implicated in the regulation of anxiety and mood.11,12,15–17 For example, hyperactivity of the HP circuit increased depression-like behaviors in rats,18 and GABAB and CB1 receptor actions at the HP synapse regulated fear behavior and the expression of aversive memory.19,20 Recent behavioral pharmacology studies also revealed a role for MHb MOR expression in opioid dependence. The gene discussed is OPRM1; the disease is depressive disorder.