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

Abstract

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 D 2 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 D 2 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 D 2 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 D 2 receptor control, whereas release in the respective axon terminal region (NAc) was controlled strongly by autoinhibition. Thus, these data indicate that, first, autoinhibition via D 2 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, D 2 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.

Somatodendritic dopamine release: recent mechanistic insights

“…This voltammetric method allows detection of evoked release of DA in discrete brain regions, including the SNc and VTA [17][18][19]21,25,26,32,38,[67][68][69]. Identification of DA can be confirmed by its characteristic voltammogram (figure 2) [18,22], as well as by amplification of the release response by inhibition of the DA transporter (DAT) [20,21], or suppression of release following inhibition of the vesicular monoamine transporter, VMAT2 [17].…”

“…In SNc and VTA, locally released DA binds to D2 autoreceptors to regulate the rate and pattern of firing of the DA neurons [23,[33][34][35][36], thereby regulating distal release of DA in dorsal and ventral striatum [37]. Local autoinhibition via DA and D2 receptors provides feedback to limit somatodendritic DA release as well [38].…”

α6-Containing Nicotinic Acetylcholine Receptors Dominate the Nicotine Control of Dopamine Neurotransmission in Nucleus Accumbens

“…DA release was evoked by a surface, bipolar concentric electrode (25 mm diameter Pt/Ir; FHC, USA) B100 mm from the recording electrode (Cragg, 2003;Cragg and Greenfield, 1997;Rice and Cragg, 2004). Stimulus pulses (200 ms duration) were generated out-of-phase with FCV scans at currents (0.5-0.7 mA) that generate maximal DA release with a single pulse.…”

“…Stimulus pulses (200 ms duration) were generated out-of-phase with FCV scans at currents (0.5-0.7 mA) that generate maximal DA release with a single pulse. Release is Ca 2 + -dependent and TTXsensitive (ie action potential-dependent) (Cragg, 2003;Cragg and Greenfield, 1997).…”

Nociceptin/Orphanin FQ Modulates Motor Behavior and Primary Motor Cortex Output Through Receptors Located in Substantia Nigra Reticulata

“…It is possible that a low degree of NOP receptor stimulation reduces dendritic DA release in SN. This would remove the inhibitory feedback mediated by somatodendritic D 2 autoreceptors (Cragg and Greenfield, 1997;Bustos et al, 2004) and result in a facilitation of rat locomotion (Bergquist et al, 2003). Alternatively, as shown for classical opioids (Johnson and North, 1992), low N/OFQ doses may preferentially inhibit GABA interneurons leading to disinhibition of nigral DA neurons (Cobb and Abercrombie, 2002).…”