GABA(B) modulation of dopamine release in the nucleus accumbens core

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dc.contributor.authorPuil, Ernest
dc.contributor.authorPitman, Kimberley A.
dc.contributor.authorBorgland, Stephanie L.
dc.date.accessioned2021-04-09T21:29:01Z
dc.date.available2021-04-09T21:29:01Z
dc.date.issued2014-11
dc.description.abstractModulation of the concentration of dopamine (DA) released from dopaminergic terminals in the nucleus accumbens (NAc) influences behaviours such as the motivation to obtain drugs of abuse. γ-Aminobutyric acid type B (GABAB ) receptors are expressed throughout the mesolimbic circuit, including in the NAc, and baclofen, an agonist of GABAB receptors, can decrease drug-seeking behaviours. However, the mechanism by which GABAB receptors modulate terminal DA release has not been well studied. We explored how baclofen modulates the concentration of DA released from terminals in the NAc core using fast-scan cyclic voltammetry in brain slices from adult male C57BL/6J mice. We found that baclofen concentration-dependently decreased single pulse-evoked DA release. This effect was blocked by the GABAB antagonist, CGP 52432, but not by a nicotinic acetylcholine receptor antagonist. Suppression of DA release by a saturating concentration of baclofen was sustained for up to 1 h. The effect of baclofen was reduced with electrical stimulations mimicking burst firing of DA neurons. Similar to the D2 receptor agonist, quinpirole, baclofen reduced the probability of DA release, supporting a mechanistic overlap with D2 receptors. Baclofen-mediated suppression of DA release persisted after a locomotor-sensitizing cocaine treatment, indicating that GABAB receptors on DA terminals were not altered by cocaine exposure. These data suggest that baclofen-mediated suppression of terminal DA release is due to GABAB activation on DA terminals to reduce the probability of DA release. This effect does not readily desensitize, and persists regardless of chronic cocaine treatment.en_US
dc.identifier.citationPitman, K.A., Puil, E., Borgland, S.L. (2014). GABA(B) modulation of dopamine release in the nucleus accumbens core. European Journal of Neuroscience, 40(10), 3472-3480. https://doi.org/10.1111/ejn.12733en_US
dc.identifier.doihttp://dx.doi.org/10.1111/ejn.12733en_US
dc.identifier.issn1460-9568
dc.identifier.urihttp://hdl.handle.net/1880/113212
dc.identifier.urihttps://doi.org/10.11575/PRISM/43748
dc.language.isoengen_US
dc.publisherWileyen_US
dc.publisher.departmentOtheren_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.hasversionsubmittedVersionen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.policyhttps://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.htmlen_US
dc.subjectDrugs of abuseen_US
dc.subjectDopamineen_US
dc.subjectGABAen_US
dc.titleGABA(B) modulation of dopamine release in the nucleus accumbens coreen_US
dc.typejournal articleen_US
ucalgary.item.requestcopytrueen_US
ucalgary.scholar.levelFacultyen_US
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