Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats

Abstract

d-Amphetamine and phencyclidine (PCP) have both been reported to produce manic-like sequela in humans, effects that are reportedly antagonized by lithium. To test the hypothesis that the acute effects of these drugs in rats may serve as models of mania, the behaviors induced by d-amphetamine (3 mg/kg) or PCP (5 mg/kg) were quantified on behavioral rating scales subsequent to chronic dietary pretreatment with lithium carbonate or control diet. On day 14 of pretreatment, PCP-induced stereotyped behaviors and ataxia were potentiated in rats receiving lithium (plasma levels 1.0 +/- 0.23 mEq/l). PCP-induced locomotor activity was not affected by lithium pretreatment. Stereotypies and locomotion induced by d-amphetamine were also not significantly affected by lithium pretreatment. These results suggest that neither PCP nor amphetamine administered acutely to rats will be useful models to explore the manic-like symptoms produced by these drugs in humans.

β-Catenin Overexpression in the Mouse Brain Phenocopies Lithium-Sensitive Behaviors

“…However, mixed results have been found regarding the effect of lithium on stimulant-induced stereotypy. Within rat studies, lithium has been found to decrease amphetamine-induced stereotypy (Flemenbaum, 1977), to have no effect on it (Fessler et al, 1982;Wielosz, 1976), or to potentiate it (Miyauchi et al, 1981), but both the dose and the isomer of amphetamine varied between the studies. There was no consistent association with strain, as all three possible outcomes were found even among Sprague-Dawley rats.…”

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

“…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).…”

“…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.…”

“…The heterogeneity of testing materials and methods may be a reason why no consensus exists on the effects of lithium on stereotypy. Within the studies of rats, lithium has been found to decrease amphetamine-induced stereotypy (Flemenbaum, 1977), to have no effect on it (Wielosz, 1976;Fessler et al, 1982), or to potentiate it (Miyauchi et al, 1981), but both the dose and the isomer of amphetamine varied between the studies. There was no consistent association with strain, as all three possible outcomes were found even among Sprague-Dawley rats.…”

Comparing Oral Lithium Carbonate and Intraperitoneal Lithium Chloride Chronic Administrations on Rats’ Activity Levels

“…A concern for controlling lithium serum levels and for avoiding tissue damage has led several researchers to favor the administration of lithium in the diet, either as chloride or carbonate, instead of the intraperitoneal route. Diet formulations differ among studies [6,[11][12][13]17]. With respect to the chronic administration of lith ium carbonate orally, the contemporary literature most commonly refers to the use of a diet containing 2.3-3.4 g of lithium carbonate mixed with 1,500 g Purina lab chow…”