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

Abstract.

Rationale: Dopamine dysfunction in the nucleus accumbens is thought to underlie the altered propensity of isolation-reared rats to self-administer psychomotor stimulants. Objective: To identify specific changes in monoamine and glutamate function in the nucleus accumbens and c-fos induction in the amygdala and striatum which may be correlated with altered cocaine self-administration in isolates. Methods: In three separate studies, group-reared and isolation-reared rats were trained to self-administer cocaine (0.083, 0.25 or 1.5 mg/kg per IV infusion; FR1), intracerebral microdialysis was used to measure cocaine-induced changes in extracellular levels of dopamine, serotonin and glutamate in the nucleus accumbens and the expression of the immediate-early gene c-fos was quantified using quantitative immunocytochemistry of its protein product Fos in several amygdala and striatal brain regions following cocaine administration. Results: Isolation-reared rats showed an enhanced sensitivity to self-administer the lowest dose of cocaine but showed retarded acquisition at the highest dose. Isolation rearing produced no effect on basal levels of dopamine, serotonin or glutamate in the nucleus accumbens but potentiated the increase in dopamine efflux, though not serotonin efflux, induced by cocaine. Cocaine increased FOS expression in most amygdala and striatal brain regions examined that were relatively greater in 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 nucleus of the amygdala. Conclusion: These data are consistent with the hypothesis that isolation rearing produces enduring changes in the sensitivity of dopamine-mediated functions in amygdala-striatal circuitry that may be directly related to the altered reinforcing properties of cocaine and other psychomotor stimulants.