¹Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

Correspondence: Dr M Basselin, Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg 9, Room 15128, Bethesda, MD 20892, USA. Tel: +1 301 594 5522; Fax: +1 301 402 0074; E-mail: mirvasln@mail.nih.gov

Received 7 July 2004; Revised 10 November 2004; Accepted 7 December 2004; Published online 6 April 2005.

Abstract

We studied the effect of lithium chloride on dopaminergic neurotransmission via D₂-like receptors coupled to phospholipase A₂ (PLA₂). In unanesthetized rats injected i.v. with radiolabeled arachidonic acid (AA, 20:4 n-6), regional PLA₂ activation was imaged by measuring regional incorporation coefficients k^* of AA (brain radioactivity divided by integrated plasma radioactivity) using quantitative autoradiography, following administration of the D₂-like receptor agonist, quinpirole. In rats fed a control diet, quinpirole at 1 mg/kg i.v. increased k^* for AA significantly in 17 regions with high densities of D₂-like receptors, of 61 regions examined. Increases in k^* were found in the prefrontal cortex, frontal cortex, accumbens nucleus, caudate–putamen, substantia nigra, and ventral tegmental area. Quinpirole, 0.25 mg/kg i.v. enhanced k^* significantly only in the caudate–putamen. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, neither 0.25 mg/kg nor 1 mg/kg quinpirole increased k^* significantly in any region. Orofacial movements following quinpirole were modified but not abolished by LiCl feeding. The results suggest that downregulation by lithium of D₂-like receptor signaling involving PLA₂ and AA may contribute to lithium's therapeutic efficacy in bipolar disorder.