Cocaine self-administration behavior can be reduced or potentiated by the addition of specific dopamine concentrations in the nucleus accumbens and amygdala using in vivo microdialysis.

Potentiation of mesolimbic dopamine levels is generally hypothesized to be reinforcing and contribute to the self-administration of addictive drugs such as cocaine. In the present study, the in vivo microdialysis technique was used to directly manipulate extracellular dopamine concentrations in the nucleus accumbens (NAC) shell and the amygdala (AMY) in rats maintaining stable patterns of cocaine (1.5 mg/kg/infusion) intake under a fixed ratio 1 schedule of reinforcement. In the NAC, a perfusate dopamine concentration of 90 nM was found to reduce cocaine self-administration, whereas a perfusate concentration of 450 nM increased the intake of cocaine. In the AMY, 45 nM perfusate dopamine inhibited cocaine self-administration, whereas 90 nM perfusate dopamine enhanced cocaine intake. The attenuation or potentiation of cocaine intake behavior was maintained throughout the time period (30 or 60 min) of the manipulation of the perfusate dopamine (DA) concentrations in the NAC and AMY. Other perfusate concentrations tested, 180 and 360 nM, in both the nucleus accumbens and amygdala, were without effect on altering the stable pattern of cocaine self-administration behavior. Overall, these experiments show that elevated mesolimbic dopamine concentrations can differentially modulate cocaine self-administration behavior.