Opposing roles for dopamine and serotonin at presynaptic receptors in the ventral tegmental area

Clinical and Experimental Pharmacology & Physiology
D L Cameron, J T Williams

Abstract

1. Dopamine D1 and 5HT1D 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 GABAB IPSP, and their 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 GABAB IPSP. This action was mimicked by 5HT and the 5HT1D agonist sumatriptan, and attenuated by the 5HT1D/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 ...Continue Reading

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Citations

Feb 20, 2009·Psychopharmacology·Paul J MeyerSusan L Ingram
Apr 30, 2009·Annual Review of Neuroscience·Peter Dayan, Quentin J M Huys
Mar 26, 2016·Progress in Neurobiology·Philippe De Deurwaerdère, Giuseppe Di Giovanni
Feb 12, 2005·Biological Psychiatry·Mauro FedericiNicola B Mercuri
Oct 20, 2006·Pharmacology & Therapeutics·K D Alex, E A Pehek
Oct 15, 2009·Journal of Psychopharmacology·Stefano PallantiEric Hollander
Aug 4, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jennifer L AmatoBryan K Yamamoto
Mar 16, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Amy Cecilia SandersXiaoxi Zhuang
Jul 1, 2004·The Journal of Pharmacology and Experimental Therapeutics·L E O'Dell, L H Parsons
May 30, 2021·Journal of Psychopharmacology·Samantha N ScottJanet L Neisewander

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