Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sensitive, calcium dependent, and blocked by a D2 receptor antagonist. Inhibition of monoamine transporters prolonged the IPSC, indicating that the time course of dopamine neurotransmission is tightly regulated by reuptake. Changing the stimulus intensity altered the amplitude but not the time course of the IPSC, whose onset was faster than could be reproduced with iontophoresis. The results indicate a rapid rise in dopamine concentration at the D2 receptors, suggesting that dopamine that is released by a train of action potentials acts in a localized area rather than in a manner consistent with volume transmission.
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We are grateful for our collaborators at the University of Washington: Richard Palmiter, Bethany Sotak, and Siobhan Robinson, who made possible the DD mouse experiments. We would also like to thank Heather Drought and Katherine Suchland for their technical assistance; and Malcolm Low, Susan Ingram, and Craig Jahr for helpful suggestions. This work was supported by NIH grants DA16467 (M.J.B); DA4523 (J.T.W); DK7680 (R.H. Goodman); MH67497, MH66360, and DA12062 (D.K.G); and MH61933 (K.W.).