Cocaine produces low dose locomotor depressant effects in NBR and F344 rats.

Recently, cocaine has been shown to produce a significant locomotor depressant effect in mice at doses of 0.1-3.0 mg/kg. These low doses are below those associated with the well-described locomotor stimulant effects of cocaine, and represent a highly potent effect of this drug. It was postulated that these low doses of cocaine which depress locomotor activity do so via inhibition of serotonin uptake, resulting in potentiation of serotonergic activity. One important means of validating and extending novel findings is to determine the species generality of an effect. Thus the present study examined the effects of low doses of cocaine on locomotor activity in two rat strains, the NBR and F344. Cocaine produced low dose locomotor depressant effects in both rat strains. However, NBR rats showed a three-fold greater sensitivity to the depressant effects of cocaine relative to F344 rats, with ED50 values being 0.73 and 2.2 mg/kg for the two strains, respectively. As the dose of cocaine increased, activity for rats of both strains returned to baseline, but at the highest doses, large increases in locomotor activity were found only in the NBR rats. These results extend the conditions over which low doses of cocaine have been shown to depress locomotor activity to an additional mammalian species, namely rats, and confirm that significant genetic differences exist in the extent and expression of this effect.