Goal-directed behavior is believed to involve interactions of prefrontal cortical and limbic inputs in the nucleus accumbens (NAcc), and their modulation by mesolimbic dopamine (DA) seems to be of primary importance in NAcc function. Using in vivo electrophysiological recordings simultaneously with DA system manipulation in rats, we show that tonic and phasic DA release selectively modulates hippocampal and prefrontal cortical inputs through D1 and D2 receptors, respectively. In addition, we also found that D1 activation and D2 inactivation in the NAcc produced behaviorally selective effects (learning versus set shifting of response strategy) that correspond to specific afferents. These results suggest that the dynamics of DA release regulate the balance between limbic and cortical drive through activation and inactivation of DA receptor subtypes in the accumbens, and this regulates goal-directed behavior.
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We thank N. Macmurdo and C. Smolak for technical assistance, B. Lowry for data acquisition software and A. West and M. Takita for suggestions on reverse microdialysis technique. This work was supported by US National Institute of Mental Health MH57440 (A.A.G.) and a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (Y.G.). Y.G. is a NARSAD Essel Investigator.
The authors declare no competing financial interests.
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