ROLE OF EXCITATORY AMINO-ACIDS IN THE VENTRAL TEGMENTAL AREA FOR CENTRAL ACTIONS OF NONCOMPETITIVE NMDA-RECEPTOR ANTAGONISTS AND NICOTINE

The putative role of non-NMDA excitatory amino acid (EAA) receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA) re lease in the nucleus acumbens (NAC) and the behavioural stimulation in duced by systemically administered dizocilpine (MK-801) was investigat ed. Microdialysis was utilized in rats with probes in the VTA and NAC. The VTA was perfused with the AMPA and kainate receptor antagonist CN QX (0.3 or 1.0 mM) or vehicle and dialysates from the NAC were analyze d with high-performance liquid chromatography for DA. Forty min after onset of CNQX or vehicle perfusion of the VTA MK-801 (0.1 mg/kg) was i njected subcutaneously (sc). Subsequently, typical MK-801 induced beha viours were assessed. The MK-801 induced hyperlocomotion was associate d with a 50% increase of DA levels in NAC dialysates. Both the MK-801 evoked hyper-locomotion and DA release in the NAC were effectively ant agonized bp CNQX perfusion of the VTA. However, by itself the CNQX or vehicle perusion of the VTA did not affect DA levels in NAC or the rat ed behaviours. The results indicate that MK-801 induced hyperlocomotio n and increased DA release in the NAC are largely elicited within the VTA via activation of non-NMDA EAA receptors, tentatively caused by lo cally increased EAA release. In contrast, the enhanced DA output in th e NAC induced by systemic nicotine (0.5 mg/k sc) was not antagonized b y intra VTA infusion of CNQX (0.3 or 1.0 mM), but instead by infusion of the NMDA receptor antagonist AP-5 (0.3 or 1.0 mM) into the VTA, whi ch by itself did not alter DA levels in the NAC. Thus, the probably in direct, EAA mediated activation of the mesolimbic DA neurons in the VT A by MK-801 and nicotine, respectively, seems to be mediated via diffe rent glutamate receptor subtypes.