OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS INTHE VENTRAL TEGMENTAL AREA

1, Dopamine D-1 and 5HT(1D) receptors are found on the terminals of af ferent GABA neurons that synapse on the ventral tegmental area (VTA) d opamine neurons. The role of these receptors in the actions of cocaine was investigated using intracellular recordings in a brain slice prep aration, Synaptic potentials were generated in the slice and GABA-medi ated inhibitory post-synaptic potentials (IPSP) were identified. 2. St imulation of dopamine D-1 receptors selectively enhanced the GABAB IPS P, and this effect was blocked by D-1 antagonists, The magnitude of th e IPSP was decreased when D-1 antagonists were applied in isolation, s uggesting tonic D-1 receptor stimulation via dendritically released do pamine. 3. Cocaine had an opposite effect and selectively decreased th e magnitude of the GABAB IPSP. This action was mimicked by 5HT and the 5HT(1D) agonist sumatriptan, and attenuated by the 5HT(1D/2C) antagon ist, metergoline. The action of cocaine was also mimicked by the 5HT-r eleasing agent, fenfluramine, and blocked by pre-incubation of the sli ce with the 5HT-depleting agent, para-chloroamphetamine. 4. The result s of this study suggest that dopamine and 5HT have opposing roles in m odulating GABA input into VTA dopamine neurons, The actions of cocaine on this interplay may have implications for understanding its addicti ve properties.