Chronic Cocaine Injections Attenuate Behavioral Response of κ-Opioid Receptors to U-50,488H Agonist

Chronic injections of cocaine (20 mg/kg daily for 10 days) increase activity and decrease anxiety in male C57Bl/6j mice in comparison with animals chronically injected with normal saline. U-50,488H (κ-opioid receptor agonist; 2.5 mg/kg) produced an anxiolytic effect in animals preinjected with normal saline and had no effect in animals chronically injected with cocaine. Presumably, chronic activation of dopaminergic systems caused by cocaine injections is paralleled by desensitization of k-opioid receptor system.