Lithium prevention of amphetamine-induced ?manic? excitement and of reserpine-induced ?depression? in mice: Possible role of 2-phenylethylamine

Abstract

Repeated treatment of mice with lithium chloride (45 mg/kg, i.p., daily for 8 days) reduced the jumping, fighting, stereotypies, and hyperactivity induced by d-amphetamine (5 mg/kg, i.p.). Lithium also reduced the hypoactivity observed 1--3 h after reserpine (0.75 mg/kg, i.p.). In biochemical studies we found that 8-day treatment with lithium markedly reduced (to 45% of control) the recovery from brain of labelled 2-phenylethylamine (PEA) following i.p. injection of labelled L-phenylalanine, while decreasing recovery from brain of labelled PEA following its i.p. injection of 63% of control. In saline-treated mice, d-amphetamine appeared to increase PEA synthesis and to accelerate its disposition, whereas reserpine enhanced PEA synthesis and reduced disposition; all of these effects were antagonized by lithium pretreatments. Since PEA appears to be one of the most powerful behavioral stimulants among endogenous neuroamines, and because its deaminated metabolites are behavioral depressants, such antagonism of brain PEA metabolism may significantly contribute to the prophylactic action of lithium against both manic and depressive behavior.

Strain Differences in Lithium Attenuation of d-Amphetamine-Induced Hyperlocomotion: A Mouse Model for the Genetics of Clinical Response to Lithium

“…In 1971, Cox et al (1971) reported that lithium attenuated stimulant-induced hyperlocomotion in rats. This effect was later reported in mice (Berggren et al, 1978;Borison et al, 1978). Because the administration of dopaminergic stimulants to rodents induces a characteristic increase in activity, and because this activity is attenuated by lithium administration, the hyperlocomotion model may provide insight into the clinical endophenotype described above.…”

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

“…While exceptions in the literature exist, they can often be attributed to an inappropriate dose of either amphetamine or lithium. As mentioned above, a decrease in hyperlocomotion is often concomitant with a rise in stereotypy at higher doses of amphetamine; this fact is likely the reason why Ebstein and colleagues found no effect of lithium on amphetamine-induced hyperlocomotion in rats, as they used doses of amphetamine ranging from 5 to 15mg/kg, the lowest of which is itself a dose high enough to elicit considerably stereotypy (Borison et al, 1978;Ebstein et al, 1980;Fessler et al, 1982). At this elevated dose, stereotypy was likely to be a confounding factor in the measure of hyperlocomotion.…”

“…Such automatic methods have the advantage of eliminating subjectivity over observer-based scoring common prior to technological advances. Indeed, some data have been acquired using observation alone to evaluate hyperlocomotion, often making use of rating scales which allow the rater to evaluate locomotor activity and stereotypy simultaneously (Borison et al, 1978;Fessler et al, 1982).…”

“…Specifically, in 1971 Cox and colleagues first reported lithium attenuation of stimulant-induced hyperlocomotion in rats (Cox et al, 1971). This effect of lithium was soon found to exist in mice as well, and results in both species have been widely replicated (Berggren et al, 1978;Borison et al, 1978) (Table 3). While exceptions in the literature exist, they can often be attributed to an inappropriate dose of either amphetamine or lithium.…”

“…Lithium administered i.p. for eight days to mice, and in chow for 21 days for rats, was effective at reducing reserpine-induced hypolocomotion (Borison et al, 1978;Lerer et al, 1980) (Table 8). Chronic lithium has also been shown to decrease hypoactivity induced by isolation in mice (Frances et al, 1981b), by immobilization in rats (Kofman et al, 1995), and by shock exposure in rats (Hines, 1986a) (Table 8).…”