THE ROLE OF AFFERENTS TO THE VENTRAL TEGMENTAL AREA IN THE HANDLING STRESS-INDUCED INCREASE IN THE RELEASE OF DOPAMINE IN THE MEDIAL PREFRONTAL CORTEX - A DUAL-PROBE MICRODIALYSIS STUDY IN THE RAT-BRAIN

This study was aimed to identify the neuronal pathways that mediate th e handling stress induced increase in the release of dopamine in the m edial prefrontal cortex (mPFC) of the rat brain. For that purpose a mi crodialysis probe was implanted in the ventral tegmental area (VTA) an d a second probe was placed in the ipsilateral mPFC. Receptor specific compounds acting on GABA(A) (20 mu M muscimol), GABA(B) (50 mu M bacl ofen), acetylcholine (100 mu M atropine, 100 mu M mecamylamine), NMDA (30, 100 and 300 mu M CPP; 300 mu M AP-5, 1 mM (+)-HA-966) and non-NMD A receptors (500 mu M CNQX) were infused into the VTA by retrograde di alysis, whereas extracellular dopamine was recorded in the ipsilateral mPFC. Intrategmental infusion of muscimol, baclofen, CPP, AP-5, (+)-H A-966 and CNQX decreased extracellular dopamine in the ipsilateral mPF C; atropine and mecamylamine were without effect on the basal values. During infusion of the various compounds rats were gently handled for 15 min. The infusions of muscimol, atropine, mecamylamine and(+)-HA-96 6 did not modify the handling stress induced increase in extracellular dopamine in the mPFC. However, during intrategmental infusion of bacl ofen, CPP, AP-5 and CNQX the handling stress induced increase in extra cellular dopamine (expressed as % of controls) in the mPFC was suppres sed. These results indicate that a glutamatergic projection to the VTA , acting via both NMDA and non-NMDA-glutamate receptors, play a major role in the handling stress-induced increase in dopamine release in th e mPFC. In addition the results suggest a certain role for GABAergic n eurones, acting via GABA(B) receptors, in the handling response. (C) 1 998 Elsevier Science B.V.