Pretreatment with corticosterone attenuates the nucleus accumbens dopamine response but not the stimulant response to cocaine in rats

It has been suggested that stress, via corticosterone secretion, can modulate some of the behavioural responses to cocaine. In particular, we have demonstrated that daily exposure to electric footshock stress or daily pretreatment with corticosterone shifts the ascending limb of the dose-response curve for the acquisition of cocaine self-administration upwards and to the left. It has been suggested that this corticosterone-induced increase in sensitivity to low doses of cocaine is associated with an enhancement of dopaminergic neurotransmission. The present study was designed to test this hypothesis. Adult male rats were pretreated with corticosterone (2.0 mg/kg intraperitoneally) 15 min prior to an injection of cocaine (5.0, 10.0 or 20.0 mg/kg intraperitoneally), and motor activity and extracellular dopamine concentrations in the nucleus accumbens were monitored. Cocaine administration resulted in dose-related increases in motor activity that were unaffected by pretreatment with corticosterone. However, rather than augmenting cocaine-induced increases in dopamine in the nucleus accumbens, corticosterone pretreatment actually caused attenuation at the two highest doses of cocaine tested. These data suggest dissociation between locomotor activation and nucleus accumbens dopamine responses to cocaine, and indicate that other brain regions and/or mechanisms may be involved in the changes in sensitivity to cocaine induced by corticosterone. (C) 2002 Lippincott Williams Wilkins.