ELECTRICAL-STIMULATION OF THE PREFRONTAL CORTEX INCREASES CHOLECYSTOKININ, GLUTAMATE, AND DOPAMINE RELEASE IN THE NUCLEUS-ACCUMBENS - AN IN-VIVO MICRODIALYSIS STUDY IN FREELY MOVING RATS

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cho lecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accu mbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was int ensity-dependent at 250-700 mu A. NAS Glu and DA levels were each elev ated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and h omovanillic acid were increased by stimulation at 100-400 Hz. When rat s were trained to lever press for mPFC stimulation, the stimulation in duced similar elevations of each of the three transmitters to those se en with experimenter-administered stimulation. Perfusion of 1 mM kynur enic acid (Kyn) into either the ventral tegmental area (VTA) or NAS bl ocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induce d by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when p erfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence fo r the existence of a releasable pool of CCK in the NAS originating fro m the mPFC. Although dopamine is the transmitter most closely linked t o reward function, it was CCK that showed frequency-dependent differen ces in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, cor eleased CCK may modulate the impact of the glutamatergic action in thi s behavior.