Methamphetamine self-administration in mice decreases GIRK channel-mediated currents in midbrain dopamine neurons.

Autor:	Sharpe AL; Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas (Dr Sharpe, L. Bettinger); Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Sharpe, E. Varela, and Dr Beckstead); Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Beckstead)., Varela E; Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas (Dr Sharpe, L. Bettinger); Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Sharpe, E. Varela, and Dr Beckstead); Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Beckstead)., Bettinger L; Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas (Dr Sharpe, L. Bettinger); Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Sharpe, E. Varela, and Dr Beckstead); Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Beckstead)., Beckstead MJ; Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, Texas (Dr Sharpe, L. Bettinger); Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Sharpe, E. Varela, and Dr Beckstead); Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas (Dr Beckstead). beckstead@uthscsa.edu.
Jazyk:	angličtina
Zdroj:	The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2014 Oct 31; Vol. 18 (5). Date of Electronic Publication: 2014 Oct 31.
DOI:	10.1093/ijnp/pyu073
Abstrakt:	Background: Methamphetamine is a psychomotor stimulant with abuse liability and a substrate for catecholamine uptake transporters. Acute methamphetamine elevates extracellular dopamine, which in the midbrain can activate D2 autoreceptors to increase a G-protein gated inwardly rectifying potassium (GIRK) conductance that inhibits dopamine neuron firing. These studies examined the neurophysiological consequences of methamphetamine self-administration on GIRK channel-mediated currents in dopaminergic neurons in the substantia nigra and ventral tegmental area. Methods: Male DBA/2J mice were trained to self-administer intravenous methamphetamine. A dose response was conducted as well as extinction and cue-induced reinstatement. In a second study, after at least 2 weeks of stable self-administration of methamphetamine, electrophysiological brain slice recordings were conducted on dopamine neurons from self-administering and control mice. Results: In the first experiment, ad libitum-fed, nonfood-trained mice exhibited a significant increase in intake and locomotion following self-administration as the concentration of methamphetamine per infusion was increased (0.0015-0.15mg/kg/infusion). Mice exhibited extinction in responding and cue-induced reinstatement. In the second experiment, dopamine cells in both the substantia nigra and ventral tegmental area from adult mice with a history of methamphetamine self-administration exhibited significantly smaller D2 and GABAB receptor-mediated currents compared with control mice, regardless of whether their daily self-administration sessions had been 1 or 4 hours. Interestingly, the effects of methamphetamine self-administration were not present when intracellular calcium was chelated by including BAPTA in the recording pipette. Conclusions: Our results suggest that methamphetamine self-administration decreases GIRK channel-mediated currents in dopaminergic neurons and that this effect may be calcium dependent. (© The Author 2015. Published by Oxford University Press on behalf of CINP.)
Databáze:	MEDLINE
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