Lithium and central monoamine neurotransmitter systems

Abstract

Ahluwalia, P., and R.L. Singhal: Lithium and central monoamine neurotransmitter systems. Drug Dev. Res. 3:111-122, 1983. Lithium salts have been in use in psychiatric medicine for the past three decades, but their mechanism of action is still unknown. Studies using a model of mania to delineate the means by which they exert their therapeutic effect have been hampered by the lack of a suitable animal analogue, although attempts have been made to induce a "manic" state in rodents. For this reason, most investigations of the neurochemical basis of lithium action have used normal animals, and have focused primarily on the monoaminergic neurotransmitters, mainly because of the predominant theory of affective disorders (the "biogenic amine hypothesis"). Data indicate that these neurotransmitter substances are affected by 112 Ahluwalia and Singhal lithium administration, although the findings are not always consistent and it is therefore difficult to determine exactly their role in the antimanic effect of lithium and the pathogenesis of the bipolar affective disorder. While animal studies have confirmed the existence of a "withdrawal" phenomenon, the involvement of biogenic amines or of central y-aminobutyric acid (GABAfminergic system in the rapid recurrence of psychotic symptoms soon after cessation of lithium therapy is still equivocal.

Lithium and bupropion antagonise the phasic changes in locomotor activity caused by dopamine infused into the rat nucleus accumbens

“…Lithium is established as being perhaps the most useful therapy for the manic phase of bipolar illness, and yet the mechanism and site of its action remain unknown (see reviews by Samuel and Gottesfeld 1973;Shopsin and Gershon 1978;Fieve and Meltzer 1978;Shaw 1981;Ahluwalia and Singhal 1983). It has been hypothesised that the manic Offprint requests to : B. Costal1 phase may reflect the release of dopamine whose effects may be exaggerated by an action on" supersensitive" dopamine receptors that have developed during the depressive phase of the cycle (see review by Bunney and Garland 1983).…”