Serotonin receptors contribute to dopamine depression of lateral inhibition in the nucleus accumbens

5-HT1B receptors mediate dopaminergic inhibition of vesicular fusion and GABA release from striatonigral synapses

“…The inhibitory effect of DA persisted in the presence of DA receptor antagonists and was intact in D1R-deficient mice, indicating a non-DA receptor action. Instead, we found that the effect of DA was prevented by inhibiting 5-HT1B receptors, consistent with a previous suggestion that DA decreases GABA release in the striatum by activating 5-HT1B receptors 28 . Together, our study indicates that 5-HT1B receptors mediate inhibitory DAergic actions on GABA release from MSN axons in the striatum and the midbrain, two regions involved in the DAergic control of volitional movement orchestrated by the basal ganglia.…”

“…To investigate the effect of DA and presynaptic D1Rs on GABA release in the SNr, we used two-photon microscopy to image synaptic vesicle fusion at the striatonigral synapses in brain slices and measured striatonigral GABA A currents in SNr neurons using optogenetics. Our findings indicate that D1Rs do not affect GABA release from striatonigral synapses, but that DA potently inhibits striatonigral GABA release through serotonergic 5-HT1B receptors, consistent with a recent report in striatum 28 .…”

“…The inhibitory effect of DA persisted in the presence of DA receptor antagonists and was intact in D1R-deficient mice, indicating a non-DA receptor action. Instead, we found that the effect of DA was prevented by inhibiting 5-HT1B receptors, consistent with a previous suggestion that DA decreases GABA release in the striatum by activating 5-HT1B receptors28 .Together, our study indicates that 5-HT1B receptors mediate inhibitory DAergic actions on GABA release from MSN axons in the striatum and the midbrain, two regions involved in the DAergic control of volitional movement orchestrated by the basal ganglia.Inhibition of striatonigral GABA release by DA depends on regulation of presynaptic Ca 2+ influx and 5-HT1B actions.Our study revealed an inhibitory effect of DA on three crucial steps of the activity-dependent GABA release from striatonigral axons: a decreased Ca 2+ influx into striatonigral axons during synaptic activation observed through two-photon imaging of axonal GCaMP in D1-MSNs; a dose-dependent reduction in synaptic vesicle fusion quantified in two-photon images of FM1-43 destaining from striatonigral boutons; and decreased amplitude of GABA A receptor currents in SNr GABA neurons following selective optogenetic activation of D1-MSN axons.…”

“…5-HT1B receptors have been shown to mediate inhibition of striatonigral GABA release produced by serotonin 32, 33 . In addition, these receptors decrease GABAergic synaptic transmission between MSNs in the ventral striatum induced by DA 28 and inhibit GABA release from D2-MSN axons in the ventral pallidum induced by cocaine, a psychostimulant that increases extracellular DA 36 .…”

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

“…Activation of NAc D1-MSNs promotes drug reward-context associations and drug-seeking behavior; whereas, activation of D2-MSNs typically opposes these behaviors [13][14][15][16][17][18][19][20][21][22][23] . Indeed, optogenetic activation of D2-MSNs inhibits drug seeking by suppressing activity downstream brain regions, such as the dorsolateral ventral pallidum, through feedforward inhibition, while D1-MSN promotes cocaine seeking behaviors 19,[24][25][26] , and activated D2-MSNs can also directly inhibit D1-MSNs by lateral inhibition within the local microcircuit to suppress drug-related behavior 19,[27][28][29] . To add to the complexity of D1-and D2-MSN-mediated drug seeking, a subpopulation of neurons that induce the immediate-early gene, Fos, during drug conditioning are required for the expression of multiple drug behaviors [30][31][32] , and the activity of these FOS+ neurons are required for future expression of many drug behaviors.…”