Dopamine Excites Nucleus Accumbens Neurons through the Differential Modulation of Glutamate and GABA Release

Abstract

Afferent activity into the nucleus accumbens (NAc) occurs in bursts of action potentials. However, it is unclear how synapses in this nucleus respond to such bursts, or how these responses are altered by dopamine (DA). I examined the effects of DA on excitatory and inhibitory responses to trains of stimuli in rat NAc slices. Both EPSCs and IPSCs showed use-dependent depression during trains. Although DA inhibited both glutamate and GABA release in the NAc, it differentially inhibited release during trains. The inhibition of IPSCs persisted throughout the train of stimuli, whereas the inhibition of EPSCs progressively diminished. This differential modulation may be explained by a calcium-dependent change in the recovery from depression at the GABA synapses, where DA acts by decreasing Ca 2ϩ entry. Thus, at later stages of sustained stimulation, DA preferentially inhibits GABA release, producing a net excitatory effect during bursts suggesting a mechanism for enhancing the contrast between competing inputs into the NAc, as well as for affecting long-term plasticity in this structure.

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

“…EPSCs from saline-treated animals showed shortterm depression following a 25 Hz train. The amplitude of the eighth EPSC was 39.972.5% of the first (n ¼ 11, Figure 5a and b) similar to the depression seen in naive tissue (Hjelmstad, 2004). In slices from amphetamine-treated rats, the short-term depression was significantly decreased.…”

“…In the rat VTA, KOP receptors directly hyperpolarize a subset of dopamine (DA) neurons (Margolis et al, 2003), specifically those that project to the prefrontal cortex (Margolis et al, 2006). Within the NAc, KOP receptor agonists inhibit the release of glutamate (Yuan et al, 1992;Hjelmstad andFields, 2001, 2003). DA signaling in the prefrontal cortex and glutamate signaling in the NAc have both been implicated in drug relapse (Cornish and Kalivas, 2000;McFarland and Kalivas, 2001;McFarland et al, 2003).…”

Dopaminergic modulation of short-term synaptic plasticity at striatal inhibitory synapses

“…Noticeably, STD was not changed. Presynaptic inhibition without STD changes has been seen in other synapses (52,63,64). The mechanism proposed to dissociate presynaptic modulation of synaptic strength from modulation of STD includes the presence of some proteins such as parvalbumin or calcium sensors (65,66).…”

Virally Mediated Increased Neurotensin 1 Receptor in the Nucleus Accumbens Decreases Behavioral Effects of Mesolimbic System Activation

“…Mesolimbic DA and glutamatergic (prefrontal cortex, hippocampus, and amygdala) inputs converge in the NAcc and in several cases on the same medium spiny cell (O'Donnell and Grace, 1995). Hippocampal and amygdala projections into the NAcc are antagonistic (Pennartz et al, 1994), and DA can facilitate or attenuate cortical inputs (Brady and O'Donnell, 2004;Hjelmstad, 2004). Furthermore, recent experiments suggest that DA and glutamate might be released from the same midbrain cells (Chuhma et al, 2004).…”