Enhanced locomotor reactivity to apomorphine following repeated cocaine treatment

To study the involvement of postsynaptic dopamine (DA) receptors in cocaine-induced behavioral sensitization, locomotor responses to apomorphine (APO, 360 micrograms/kg, IP), a direct DA agonist, were compared in rats repeatedly treated with cocaine (15 mg/kg, IP x 5 and one challenge injection 4 days later) and saline under different environmental conditions. When cocaine was injected under activated conditions, immediately before animal placement in activity chamber, more powerful locomotor response to the initial drug and a significant effect of repeated treatment (sensitization) were found compared to drug administration under quiet conditions, 2 h after animal placement in activity chamber. In this case, locomotor response to the initial drug was similar to that of saline, and the effect of repeated injections on locomotion was absent (no sensitization). Locomotor stimulation induced by APO was significantly enhanced in both groups of cocaine-treated animals compared to saline controls. This effect, however, was more powerful in animals treated with cocaine under activated conditions. Present data suggest that enhanced responsiveness of postsynaptic DA receptors developed due to chronic cocaine treatment may contribute to stable alteration of DA transmission thought to mediate cocaine sensitization.