Modulation 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. c-Aminobutyric acid type B (GABA_B) receptors are expressed throughout the mesolimbic circuit, including in the NAc, and baclofen, an agonist of GABA_B receptors, can decrease drug-seeking behaviours. However, the mechanism by which GABA_B 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 pulseevoked DA release. This effect was blocked by the GABA_{B,/sub> 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.}

Item Type:	Refereed Article
Keywords:	GABA, dopamine, cocaine
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Central nervous system
Objective Division:	Health
Objective Group:	Public health (excl. specific population health)
Objective Field:	Public health (excl. specific population health) not elsewhere classified
UTAS Author:	Pitman, KA (Dr Kimberley Pitman)
ID Code:	102673
Year Published:	2014
Web of Science® Times Cited:	45
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2015-09-03
Last Modified:	2017-11-06
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