The effects of long-term administration of rubidium or lithium on reactivity to stress and on dopamine output in the nucleus accumbens in rats

Rubidium and lithium are alkali metals belonging to the same periodic serie s as sodium, potassium and cesium. In the present report the effects of lit hium and rubidium on animal reactivity to stressful stimuli and on dopamine output in the nucleus accumbens were studied. A dose-response curve with r ubidium, administered acutely before exposure to unavoidable stress, showed a maximal protective activity on escape deficit development at the dose of 0.41 mEq/kg. Rubidium injected at doses of 0.008-0.08 mEq/kg 72 h before t he unavoidable stress had the same efficacy as the acute 0.41 mEq/kg dose. Tolerance to the effect of rubidium developed after 9 days of treatment and , on day 15, rats presented a spontaneous escape deficit. The acute effect of lithium, administered for 3.5 days at the dose of 0.8 mEq/kg, i.p. twice a day before the exposure to unavoidable stress, was analogous to that of rubidium, but after repeated treatment a spontaneous escape deficit develop ed. Rats showing an escape deficit secondary to chronic stress also present ed decreased extraneuronal dopamine concentrations in the nucleus accumbens . Accordingly, microdialysis studies showed significantly lower extracellul ar dopamine levels in rats chronically treated with Lithium or rubidium com pared to control animals. Cocaine (5 mg/kg i.p.) administered acutely incre ased extracellular dopamine concentrations in control rats, as well as in r ats chronically stressed or chronically treated with lithium or rubidium. H owever, the dopamine increase was significantly higher in controls compared to the other groups. In conclusion, long-term treatment with lithium or ru bidium, or the exposure to chronic stress, produced a condition of behavior al hypo-reactivity accompanied by a decreased dopamine output in the nucleu s accumbens. (C) 1999 Elsevier Science B.V. All rights reserved.