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Effect of chronic lithium treatment on D_2/3 autoreceptor regulation of dopaminergic function in the rat

Lookup NU author(s): Dr Lindsey Ferrie, Dr Sasha Gartside, Professor Allan Young, Professor Richard McQuade

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Abstract

Dysregulation of mesolimbic dopamine (DA) neurotransmission has been implicated in bipolar disorder. DA release in the nucleus accumbens is reduced in rats treated chronically with the mood stabiliser lithium, and this effect is maintained for 3 days after withdrawal from the lithium treatment. We tested whether this decrease in DA release is due to an increase in D2/3 autoreceptor sensitivity. In vivo microdialysis studies showed that in the shell of the nucleus accumbens, dialysate DA was decreased following chronic lithium treatment and 3 days after withdrawal from lithium treatment. The elevation of dialysate DA induced by local blockade of the terminal D2/3 receptor was reduced in both lithium treated and lithium withdrawn groups. In vitro electrophysiology studies showed that chronic lithium treatment (and lithium withdrawal) did not alter either basal firing rate of DA neurones in the ventral tegmental area, or somatodendritic D2/3 autoreceptor-mediated inhibition of firing. D2 mRNA expression in the ventral tegmental area was unchanged by lithium treatment and lithium withdrawal. Our data suggest that the decrease in dopamine release in the nucleus accumbens induced by chronic lithium treatment is not the result of increased terminal or somatodendritic autoreceptor sensitivity or decreased firing rate of DA neurones. © 2007 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Ferrie LJ, Gartside SE, Martin KM, Young AH, McQuade R

Publication type: Article

Publication status: Published

Journal: Pharmacology Biochemistry and Behavior

Year: 2008

Volume: 90

Issue: 2

Pages: 218-225

ISSN (print): 0091-3057

ISSN (electronic): 1873-5177

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/j.pbb.2007.10.013

DOI: 10.1016/j.pbb.2007.10.013

PubMed id: 18031799

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