Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse | Macquarie University ResearchOnline

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Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse

Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/184989

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Title: Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse
Related: Synapse, Vol. 64, Issue 3, (2010), p.216-223
DOI: 10.1002/syn.20717
Publisher: John Wiley & Sons
Date: 2010
FoR/RFCD Code(s): 170200 Cognitive Sciences 110900 Neurosciences
Author/Creator: Lester, Deranda B
Author/Creator: Miller, Anthony D
Author/Creator: Blaha, Charles D
Description: The reinforcing properties of cocaine have been related to increased extracellular concentrations of dopamine in the nucleus accumbens (NAc). M5 muscarinic acetylcholine receptors (mAChRs) on dopamine cells in the ventral tegmental area (VTA) facilitate mesoaccumbens dopamine transmission and are critically involved in mediating natural and drug reinforcement. We investigated the effects of pharmacological blockade of mAChRs in the VTA on cocaine's ability to enhance electrically evoked NAc dopamine efflux. Using fixed potential amperometry together with carbon fiber recording microelectrodes positioned in the NAc core, we quantified dopamine oxidation currents (dopamine efflux) evoked by brief stimulation (15 monophasic pulses at 50 Hz every 30 s) of the laterodorsal tegmentum (LDT) in urethane (1.5 g/kg, i.p.) anesthetized mice. Compared to predrug baseline responses, cocaine (5 or 10 mg/kg, i.p.) dose-dependently enhanced LDT stimulation-evoked NAc dopamine efflux, whereas the nonsubtype selective mAChR antagonist scopolamine (10 μg/0.5 μl) microinfused into the VTA diminished LDT-evoked NAc dopamine efflux. Preinfusion of scopolamine into the VTA diminished the facilitatory actions of cocaine on LDT stimulation-evoked NAc dopamine efflux, and when infused at the peak effect of cocaine attenuated LDT-evoked dopamine efflux to below predrug baseline levels. These findings suggest that LDT cholinergic inputs to dopamine neurons in the VTA, via activation of mAChRs (probably of the M5 subtype), are involved in modulating the facilitatory effects of cocaine on NAc dopamine neurotransmission. They also suggest that the development of antagonists aimed at selectively disrupting M5 receptor function may be valuable in reducing abuse liability of psychostimulants.
Description: 8 page(s)
Subject Keyword: 170200 Cognitive Sciences
Subject Keyword: 110900 Neurosciences
Subject Keyword: fixed potential amperometry
Subject Keyword: M5 muscarinic receptor
Subject Keyword: cocaine
Subject Keyword: scopolamine
Subject Keyword: laterodorsal tegmentum
Subject Keyword: ventral tegmental area
Resource Type: journal article
Organisation: Macquarie University. Dept. of Psychology

Identifier: http://hdl.handle.net/1959.14/184989
Identifier: ISSN:1098-2396
Identifier: mq-rm-2011003010
Language: eng
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