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Information Seminar Paper

Title

BUPROPION CAN PREVENT THE EXCITATION OF VENTRAL TEGMENTAL AREA DOPAMINERGIC NEURONS MEDIATED BY GABA BLOCKED THROUGH BICUCULINE APPLICATION

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Abstract

 INTRODUCTION: THE VENTRAL TEGMENTAL AREA (VTA) IS A MAJOR BRAIN DOPAMINE (DA) SOURCE. VTA IS REGULATED BY BOTH EXTERNAL AND INTERNAL NEURONS. THE VTA GAMMA AMINO BUTYRIC ACID RECEPTORS (GABARS) AND GABAERGIC NEURONS INVOLVE IN THIS CONTROL. BUPROPION AS AN ATYPICAL ANTIDEPRESSANT CAN MODULATE VTA-DA NEURONS. THIS STUDY FOCUSED ON THE ACUTE EFFECT OF INTRACEREBROVENTRICULAR (ICV) MICRO INFUSION OF BUPROPION ON THE VTA-DA NEURONS OWING TO GABA-A RECEPTOR BLOCKADE.METHODS: MALE WISTAR RATS WERE PREPARED FOR VTA-DA NEURON RECORDING BY URETHANE ANESTHESIA. NEURONS WITH SIMPLE TONIC SPIKES THAT EXCITED BY BICUCULINE APPLICATION WERE RECORDED IN 3 BICUCULINE (5, 2.5, AND 1 MG, ICV), BUPROPION (5 ΜMG, ICV), AND 3 BICUCULINE PLUS BUPROPION GROUPS. THE CONTROL AND VEHICLE NEURONAL RECORDING WERE CHECKED FOR STABILITY OF THE EXPERIMENTS AND SHOWED NO DIFFERENCE. THE GLASS MICROELECTRODES WERE INSERTED INTO THE RIGHT VTA STEREOTAXIC ALLY AND STABLE MULTIUNITS WERE ISOLATED BY IGOR PRO SOFTWARE OFF-LINE. BUPROPION WAS MICRO INFUSED 10 MIN AFTER BICUCULINE APPLICATION. THE PSTH OF SPIKES WERE ANALYZED BY ONE-WAY ANOVA WITH LSD POST HOC TEST.RESULTS: 78 VTA-DA NEURONS THAT EXCITED BY BICUCULINE APPLICATION WERE ISOLATED. THE BICUCULINE MICRO INFUSION EXCITED THE NEURONS DOSE DEPENDENTLY WITH MAXIMUM 45.4 ± 1.56 MIN AND 178.5 ± 3.6% OF BACKGROUND FIRING RATE. BUPROPION CANCELLED THE VTA-DA NEURONS EXCITATION IN 76% COMPLETELY AND 24% PARTIALLY. THE DURATION OF BUPROPION INHIBITION LASTED UP TO 120 ± 23.7 MIN.CONCLUSIONS: THE INTRA-VTA GABA RECEPTORS THAT AGGREGATED ON THE VTA-DA NEURONS HAVE CRITICAL REGULATORY EFFECTS ON THE VTA-DA NEURONS. IT POSTULATED THAT THE BLOCKING OF THE GABA RECEPTORS DECREASE THE VTA OUTFLOW AND VICE VERSA. BUPROPION CAN INVOLVE IN THE VTA-DA NEURONAL ACTIVITY BY INTERACTION OF GABA RECEPTORS.

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