Cocaine produces locomotor stimulation in SS but not LS mice: relationship to dopaminergic function

Cocaine produces several behavioral effects, most notably locomotor stimulation. While low doses of cocaine have been shown to decrease locomotor activity, moderate to high doses in the range of 5-50 mg/kg usually produce a marked increase in locomotor activity in rodents. This study examined the effects of a range of cocaine doses, 1-75 mg/kg, on locomotor activity in LS/Ibg (LS) and SS/Ibg (SS) mice. At the lowest doses, activity was depressed in both lines, but to a greater extent in LS mice. As the dose of cocaine was increased, activity returned to baseline, and at the highest doses, increases in locomotor activity were found, but only in SS mice. In LS mice, cocaine was ineffective in increasing locomotor activity at any of the doses tested. Since striatal dopaminergic neurons influence locomotor activity, we also assessed ligand affinity and receptor density of dopamine transporters and dopaminergic D1 and D2 receptors in striatal tissue obtained from these two selected lines. No differences in these receptor binding parameters were found. However, because of their anomalous locomotor response to cocaine, LS mice may prove to be a valuable tool in increasing our understanding of those sites which mediate specific effects of cocaine.