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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pitman, Kimberley A. Puil, Ernest Borgland, Stephanie L. |
| Description | Country affiliation: Canada Author Affiliation: Pitman KA ( Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, BC, Canada) |
| Abstract | 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. 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. |
| File Format | HTM / HTML |
| ISSN | 0953816X |
| Issue Number | 10 |
| Volume Number | 40 |
| e-ISSN | 14609568 |
| Journal | European Journal of Neuroscience |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2014-11-01 |
| Publisher Place | France |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Neuroscience Baclofen Pharmacology Dopamine Metabolism Gaba-b Receptor Agonists Nucleus Accumbens Drug Effects Physiology Receptors, Gaba-b Animals Benzylamines Central Nervous System Stimulants Cocaine Dopamine Agonists Dose-response Relationship, Drug Gaba-b Receptor Antagonists Male Mice, Inbred C57bl Motor Activity Neurons Nicotinic Antagonists Phosphinic Acids Quinpirole Receptors, Dopamine D2 Agonists Tissue Culture Techniques Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience |
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