The effect of lithium administration in animal models of depression: a short review

Abstract

The aim of this short review was to collate the data involving the effects of lithium alone, or in combination, with antidepressant drugs in several animal models of depression. It has been shown that lithium administration reduced immobility in the mouse forced swimming test when given 30 min, but not 45 min, before testing. Further studies indicated that this activity was probably a result of an activity on serotonin (5-HT) 1A and 1B receptor subtypes. Lithium treatment has been shown to reverse helpless behaviour in the learned helplessness model of depression after chronic treatment (30 days), where lithium was administered in the drinking water. Further studies showed that acute (5 days) administration of lithium failed to reverse behavioural deficits. In the olfactory bulbectomised rat model of depression, several immunological and enzymatic functions have been shown to be altered and these changes are regularised by antidepressant treatment as well as lithium administration for 15 days. Hypokinesia (reduced locomotor activity) is a phenomenon observed following immobilisation stress in rats. This behavioural deficit was attenuated by lithium together with a wide range of antidepressant drugs used in the treatment of unipolar depression at non-stimulant doses. In addition, a single administration of lithium slightly inhibited midbrain raphe lesion-induced muricidal behaviour (25%); however, repeated treatment (5 days) significantly attenuated this behavioural deficit. Lithium treatment has also been shown to reverse behavioural and biochemical deficits induced by reserpine together with those induced by acute administration of single intracerebroventricular (i.c.v.) dose of the Na, K-ATPase-inhibiting compound, ouabain. Long-term studies of lithium augmentation have not been performed, so that no clear recommendations for the duration of this therapy can be made. The points raised in this short review endorse the commencement of such studies.

Lithium and cognitive enhancement: leave it or take it?

“…These findings are corroborated by animal data collected in a variety of animal models of depression Nixon et al 1994;Redrobe and Bourin 1997;Redrobe and Bourin 1999). Animal studies tend to associate this potentiating effect with increases in 5-HT neurotransmission induced by lithium treatment: more specifically, to a modulatory action of lithium on 5-HT1B autoreceptors in the cortical area, in case of acute treatment, or in the hippocampus, in case of chronic treatment (Chenu and Bourin 2006).…”

Glycogen Synthase Kinase-3β Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium

“…Lithium does not affect time immobile for rats in the FST (Hata et al, 1995;Kitamura et al, 2002;Einat et al, 2003;Wegener et al, 2003). Acute lithium injection has been reported to reduce time immobile in mice if animals are tested 30 min after injection but not at 45 min (Nixon et al, 1994;Redrobe and Bourin, 1999a). Acute lithium also reportedly enhances the effect of antidepressants on the FST (Redrobe and Bourin, 1999b).…”

Mutant mouse models of depression: Candidate genes and current mouse lines

“…Pharmacological depression models have also been established, including the use of reserpine, which depletes the aminergic pools in the presynaptic nerve terminals, imitating the pathophysiology that is postulated by the monoamine hypothesis, including anhedonia (Bourin, 1990;Almeida et al, 1998;Skalisz et al, 2002). Some effects of reserpine administration are similar to human depression and are reversed by antidepressants or ECT (Redrobe and Bourin, 1999;Vetulani et al, 1986). However, some authors consider this model as inadequate because of its lack of etiological validity and its non-specific effects on all types of monoamine neurotransmission.…”