Differential Modulation of Cocaine's Discriminative Cue by Repeated and Variable Stress Exposure: Relation to Monoamine Transporter Levels

Discriminative stimulus functions of drugs of abuse play an important role in the acquisition, maintenance and reinstatement of drug-taking behavior. The present study tested whether two different schedules of stressor presentation, i.e., repeated and variable, for 10 days, can modify the discriminative stimulus effects of cocaine in male rats trained to discriminate cocaine (10 mg/kg, i.p.) from saline. Dopamine (DAT), serotonin (SERT) and norepinephrine (NET) transporter levels in mesocorticolimbic areas were also measured using western blotting after stress exposure to determine if the relative ratio of these proteins may explain differences in behavior. Rats exposed to both repeated and variable stress displayed shifts in the cocaine dose-response curve but with different patterns of responding. In handled controls, ED(50) values for cocaine-like responding were stable after 10 days of handling compared to baseline. Repeated stress produced a transient left-ward shift in cocaine-like responding, indicating increased sensitivity to the cocaine cue. ED(50) values after variable stress did not differ from baseline, although maximal cocaine-like responding was lower at the two highest doses of cocaine tested at which variably stressed rats exhibited more saline-like responding. Alterations in DAT and NET were found in the Repeated Stress group and DAT and SERT in the Variable Stress group in select brain regions which may be responsible for differences in behavior.