Prazosin, an α-1 adrenergic antagonist, reduces cocaine-induced reinstatement of drug-seeking

Background: Norepinephrine is implicated in cocaine's behavioral effects, In this study, we tested the effect of prazosin, an alpha 1-adrenergic receptor antagonist, on cocaine-induced reinstatement of drug-seeking behavior. Methods. Rats were trained to se self-administer cocaine intravenously under a fixed-ratio 3 schedule of reinforcement. After behavior was established, cocaine was replaced with saline and behavior extinguished. The ability of cocaine (0. 5-20 mg/kg) alone or combined with prazosin (.3 mg/kg) combined with prazosin to reinstate lever press responding was tested. The effects food was examined in another set of rats. Results: Cocaine induced a dose-dependent reinstatement of drug-seeking behavior that was significantly attenuated by prazosin. This dose of prazosin did not alter lever press response rates for food. Conclusions: The attenuation in drug-induced reinstatement is likely not due to prazosin-induced suppression of activity. These results suggest alpha 1-adrenergic mechanisms contribute to reinstatement in rats and perhaps, to relapse in addicts.