Premium
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: OPPOSING ROLES FOR DOPAMINE AND SEROTONIN AT PRESYNAPTIC RECEPTORS IN THE VENTRAL TEGMENTAL AREA
Author(s) -
Cameron D. L.,
Williams J. T.
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb01947.x
Subject(s) - dopamine , ventral tegmental area , inhibitory postsynaptic potential , neuroscience , gabab receptor , chemistry , 5 ht receptor , dopamine receptor , serotonin , pharmacology , agonist , receptor , dopaminergic , biology , biochemistry
SUMMARY 1. Dopamine D 1 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 D 1 receptors selectively enhanced the GABA b IPSP, and this effect was blocked by D 1 antagonists. The magnitude of the IPSP was decreased when D 1 antagonists were applied in isolation, suggesting tonic D 1 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.