Leftward shift in the acquisition of cocaine self-administration in isolation-reared rats: relationship to extracellular levels of dopamine, serotonin and glutamate in the nucleus accumbens and amygdala-striatal FOS expression

Rationale: Dopamine dysfunction in the nucleus accumbens is thought to unde rlie the altered propensity of isolation-reared rats to self-administer psy chomotor stimulants. Objective: To identify specific changes in monoamine a nd glutamate Function in the nucleus accumbens and c-fos induction in the a mygdala and striatum which may be correlated with altered cocaine self-admi nistration in isolates. Methods: In three separate studies, group-reared an d isolation-reared rats were trained to self-administer cocaine (0.083, 0.2 5 or 1.5 mg/kg per IV infusion; FR1), intracerebral microdialysis was used to measure cocaine-induced changes in extracellular levels of dopamine, ser otonin and glutamate in the nucleus accumbens and the expression of the imm ediate-early gene c-fos was quantified using quantitative immunocytochemist ry of its protein product Fos in several amygdala and striatal brain region s following cocaine administration. Results: Isolation-reared rats showed a n enhanced sensitivity to self-administer the lowest dose of cocaine but sh owed retarded acquisition at the highest dose. Isolation rearing produced n o effect on basal levels of dopamine, serotonin or glutamate in the nucleus accumbens but potentiated the increase in dopamine efflux, though not sero tonin efflux, induced by cocaine. Cocaine increased FOS expression in most amygdala and striatal brain regions examined that were relatively greater i n isolation-reared rats in core and shell regions of the nucleus accumbens, medial and lateral regions of the dorsal striatum as well as the central n ucleus of the amygdala. Conclusion: These data ale consistent with the hypo thesis that isolation rearing produces enduring changes in the sensitivity of dopamine-mediated functions in amygdala-striatal circuitry that may be d irectly related to the altered reinforcing properties of cocaine and other psychomotor stimulants.