GABAB modulation of dopamine release in the nucleus accumbens core
journal contribution
posted on 2023-05-18, 12:40authored byKimberley Pitman, Puil, E, Borgland, SL
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 (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 pulseevoked DA release. This effect was blocked by the GABAB,/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.
History
Publication title
European Journal of Neuroscience
Volume
40
Pagination
3472-3480
ISSN
0953-816X
Department/School
Menzies Institute for Medical Research
Publisher
Blackwell Publishing Ltd
Place of publication
United Kingdom
Rights statement
Copyright 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
Repository Status
Restricted
Socio-economic Objectives
Public health (excl. specific population health) not elsewhere classified