Lithium, but not carbamazepine, potentiates hyperactivity induced by intra-accumbens cholera toxin

Pharmacology, Biochemistry, and Behavior
O KofmanJ J Warsh

Abstract

Elevated G protein abundance and/or function has been implicated in the pathophysiology and pharmacotherapy of bipolar affective disorder. To test the interactions between chronic lithium and carbamazepine on behavioral changes induced by cholera toxin (CTX), which catalyzes ADP-ribosylation and constitutively activates G alphas/olf, rats were given chronic dietary lithium, carbamazepine (CBZ), or regular food (REG) and injected bilaterally in the nucleus accumbens (nACC) with CTX (400 ng/ml/side) or vehicle. Locomotor activity was tested daily for 2 weeks after the injection. CTX increased locomotor activity, but a significant interaction between drug treatment and CTX reflected a two- to threefold increase of CTX-induced hyperactivity in the lithium-treated group. In contrast, on day 1, the CBZ-CTX group was significantly more active than the the LI-CTX and REG-CTX groups, both of which had suppressed locomotor activity. There was a significant reduction in CTX-catalyzed ADP ribosylation of G alphas (52 kDa and 45 kDa) in the nucleus accumbens in all three CTX-treated groups. The potentiation of the behavioral effect of CTX by lithium supports the hypothesis that lithium interacts with G proteins; however, the mechanism of in...Continue Reading

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Citations

Jan 31, 2004·Progress in Neuro-psychopharmacology & Biological Psychiatry·Rodrigo Machado-VieiraJair C Soares
Aug 10, 2002·Journal of Psychosomatic Research·Todd D Gould, Husseini K Manji
Oct 16, 1999·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·O Kofman, Y Patishi
Dec 1, 2002·Clinical Neuroscience Research·Todd D GouldHusseini K Manji
May 11, 2010·Neuropsychobiology·Jorge A QuirozHusseini K Manji
Nov 8, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Ajaykumar N SharmaJoao Quevedo
Oct 6, 2000·Biological Psychiatry·H K Manji, R H Lenox

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