Long‐term behavioral and neurochemical effects of chronic stress exposure in rats

Rats exposed to acute unavoidable stress develop a deficit in escaping avoidable aversive stimuli that lasts as long as unavoidable stress exposure is repeated. A 3‐week exposure to unavoidable stress also reduces dopamine (DA) output in the nucleus accumbens shell (NAcS). This study showed that a 7‐day exposure to unavoidable stress induced in rats an escape deficit and a decrease in extraneuronal DA basal concentration in the NAcS. Moreover, animals had reduced DA and serotonin (5‐HT) accumulation after cocaine administration in the medial pre‐frontal cortex (mPFC) and NAcS, compared with control animals. After a 3‐week exposure to unavoidable stress, escape deficit and reduced DA output in the NAcS were still significant at day 14 after the last stress administration. In the mPFC we observed: (i) a short‐term reduction in DA basal levels that was back to control values at day 14; (ii) a decrease in DA accumulation at day 3 followed by a significant increase beyond control values at day 14; (iii) a significant reduction in 5‐HT extraneuronal basal levels at day 3, but not at day 14. Finally, a significant decrease in 5‐HT accumulation following cocaine administration was present in the NAcS and mPFC at day 3, but not at day 14. In conclusion, a long‐term stress exposure induced long‐lasting behavioral sequelae associated with reproducible neurochemical modifications.