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GABA B modulation of dopamine release in the nucleus accumbens core
Author(s) -
Pitman Kimberley A.,
Puil Ernest,
Borgland Stephanie L.
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12733
Subject(s) - baclofen , nucleus accumbens , quinpirole , chemistry , agonist , dopaminergic , dopamine , pharmacology , receptor , gabab receptor , gabaa receptor , endocrinology , biochemistry , biology
Modulation of the concentration of dopamine ( DA ) released from dopaminergic terminals in the nucleus accumbens ( NA c) influences behaviours such as the motivation to obtain drugs of abuse. γ‐Aminobutyric acid type B ( GABA B ) receptors are expressed throughout the mesolimbic circuit, including in the NA c, 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 NA c core using fast‐scan cyclic voltammetry in brain slices from adult male C57 BL /6J mice. We found that baclofen concentration‐dependently decreased single pulse‐evoked DA release. This effect was blocked by the GABA B 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 D 2 receptor agonist, quinpirole, baclofen reduced the probability of DA release, supporting a mechanistic overlap with D 2 receptors. Baclofen‐mediated suppression of DA release persisted after a locomotor‐sensitizing cocaine treatment, indicating that GABA B receptors on DA terminals were not altered by cocaine exposure. These data suggest that baclofen‐mediated suppression of terminal DA release is due to GABA B activation on DA terminals to reduce the probability of DA release. This effect does not readily desensitize, and persists regardless of chronic cocaine treatment.