Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA

1. Dopamine D₁ and SHT_1d receptors are found on the terminals of afferent GABA neurons that synapse on the ventral tegmental area (VTA) dopamine neurons. The role of these receptors in the actions of cocaine was investigated using intracellular recordings in a brain slice preparation. Synaptic potentials were generated in the slice and GABA‐mediated inhibitory post‐synaptic potentials (IPSP) were identified. 2. Stimulation of dopamine D₁ receptors selectively enhanced the GABA_b IPSP, and this effect was blocked by D₁ antagonists. The magnitude of the IPSP was decreased when D₁ antagonists were applied in isolation, suggesting tonic D₁ receptor stimulation via dendritically released dopamine. 3. Cocaine had an opposite effect and selectively decreased the magnitude of the GABA_b IPSP. This action was mimicked by 5HT and the SHT_1d agonist sumatriptan, and attenuated by the 5HTI_1D/2c antagonist, metergoline. The action of cocaine was also mimicked by the 5HT‐releasing agent, fenfluramine, and blocked by pre‐incubation of the slice with the 5HT‐depleting agent, para‐chloroamphetamine. 4. The results of this study suggest that dopamine and 5HT have opposing roles in modulating GABA input into VTA dopamine neurons. The actions of cocaine on this interplay may have implications for understanding its addictive properties.