Effects of chronic treatment with the α2‐adrenergic agonist, lofexidine, on cocaine self‐administration

Abstract

Cocaine's abuse related effects have been attributed to its interaction with dopamine systems. Although adrenergic receptors are located in brain areas that modulate dopaminergic activity, adrenergic agents have received little attention as potential pharmacotherapies for cocaine addiction. Lofexidine, a a2‐adrenergic agonist, is being investigated as a treatment for reducing opioid withdrawal symptoms but little is known about its direct interactions with drugs of abuse. The present study assessed the effects of chronic treatment with lofexidine on cocaine selfadministration. Male rhesus monkeys were trained under a second order FR2(VR16) schedule of food and cocaine reinforcement. Chronic treatment (7 days) with lofexidine (0.1–0.32 mg/kg/hr, IV) potentiated the reinforcing effects of cocaine as evidenced by a leftward shift in the cocaine dose‐effect curve. Chronic lofexidine had no effect on food‐maintained responding and mild side effects during treatment. Fewer overt behavioral effects were also seen upon cessation of treatment compared to clonidine (0.032–0.1 mg/kg/hr, IV). Although clinical studies also find that lofexidine produces few unwanted side effects and has minimal withdrawal effects compared to clonidine, its potentiation of cocaine's reinforcing effects makes it unlikely that lofexidine will be effective for cocaine abuse treatment. Supported by NIDA DA02519 and DA026892