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Biol Psychiatry. 2005 May 15;57(10):1202-4.

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

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  • 1Division of Substance Abuse, Yale University School of Medicine, West Haven, Connecticut 06516, USA.



Norepinephrine is implicated in cocaine's behavioral effects. In this study, we tested the effect of prazosin, an alpha1-adrenergic receptor antagonist, on cocaine-induced reinstatement of drug-seeking behavior.


Rats were trained to 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) to reinstate lever press responding was tested. The effects of prazosin on lever press responding for food was examined in another set of rats.


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.


The attenuation in drug-induced reinstatement is likely not due to prazosin-induced suppression of activity. These results suggest alpha1-adrenergic mechanisms contribute to reinstatement in rats and perhaps, to relapse in addicts.

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