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Volume 17, Number 15, Issue of August 1, 1997 pp. 5738-5746
Copyright ©1997 Society for Neuroscience

Differential Autoreceptor Control of Somatodendritic and Axon Terminal Dopamine Release in Substantia Nigra, Ventral Tegmental Area, and Striatum

Received April 11, 1997; revised May 14, 1997; accepted May 15, 1997.

Stephanie J. Cragg and Susan A. Greenfield

University Department of Pharmacology, Oxford University, Oxford OX1 3QT, United Kingdom

Dopamine (DA) is released from somatodendritic sites of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), where it has neuromodulatory effects. The aim of this study was to evaluate the role of D₂ autoreceptor inhibition in the regulation of this somatodendritic release in each region. Fast cyclic voltammetry at carbon fiber microelectrodes was used to measure electrically evoked DA release in vitro. Furthermore, we compared D₂ regulation of somatodendritic release with the more familiar axon terminal release in caudate putamen (CPu) and nucleus accumbens (NAc). Evoked DA release was TTX-sensitive at all sites. There was significant D₂ autoinhibition of DA release in SNc; however, this mechanism was two- to threefold less powerful, as compared with axon terminal release in CPu. In contrast to SNc, somatodendritic release in VTA was not under significant D₂ receptor control, whereas release in the respective axon terminal region (NAc) was controlled strongly by autoinhibition. Thus, these data indicate that, first, autoinhibition via D₂ receptors consistently plays a less significant role in the control of somatodendritic than axon terminal DA release, and, second, even at the level of somatodendrites themselves, D₂ autoinhibition displays marked regional variation. In the light of previous data indicating that DA uptake processes are also less active in somatodendritic than in terminal regions, these results are interpreted as indicating that DA transmission is regulated differently in somatodendritic zones, as compared with axon terminals, and thus may have different functional consequences.

Key words: somatodendritic release; dopamine; substantia nigra; ventral tegmental area; striatum; D₂ receptor; autoreceptor

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