Cocaine and chronic stress exposure produce an additive increase in neuronal activity in the basolateral amygdala

Cocaine addiction is a chronic, relapsing disorder. Stress and cues related to cocaine are two common relapse triggers. We have recently shown that exposure to repeated restraint stress during early withdrawal accelerates the time-dependent intensification or incubation of cue-induced cocaine craving that occurs during the first month of withdrawal, although craving ultimately plateaus at the same level observed in controls. These data indicate that chronic stress exposure during early withdrawal may result in increased vulnerability to cue-induced relapse during this period. Previous studies have shown that chronic stress exposure in drug-naive rats increases neuronal activity in the basolateral amygdala (BLA), a region critical for behavioral responses to stress. Given that glutamatergic projections from the BLA to the nucleus accumbens are critical for the incubation of cue-induced cocaine craving, we hypothesized that cocaine withdrawal and chronic stress exposure produce separate increases that additively increase BLA neuronal activity. To assess this, we conducted in vivo extracellular single-unit recordings from the BLA of anesthetized adult male rats following cocaine or saline self-administration (6 h/day for 10 days) and repeated restraint stress or control conditions on withdrawal days (WD) 6-14. Recordings were conducted from WD15 to WD20. Interestingly, cocaine exposure alone increased the spontaneous firing rate in the BLA to levels observed following chronic stress exposure in drug-naive rats. Chronic stress exposure during cocaine withdrawal further increased firing rate. These studies may identify a potential mechanism by which both cocaine and chronic stress exposure drive cue-induced relapse vulnerability during abstinence.

Automated summary

Chronic stress exposure during early withdrawal may increase vulnerability to cue-induced relapse, while cocaine withdrawal and chronic stress exposure separately increase BLA neuronal activity. These findings suggest a potential mechanism by which both cocaine and chronic stress drive cue-induced relapse vulnerability during abstinence.