Chronic administration of a norepinephrine antagonist prevents and partially reverses escalation of cocaine self‐administration

Abstract

AbstractAnxiety is a critical component of the development and maintenance of drug addiction; however, anti‐anxiety medications such as benzodiazepines and beta‐blockers (β‐adrenergic receptor antagonists) are not used for the treatment of substance use disorder, except for the management of acute withdrawal syndrome. Preclinical studies have shown that beta‐blockers may reduce stress‐induced relapse; however, the effect of beta blockers on the escalation and maintenance of drug intake has not been tested. To address this issue, we chronically administered the β‐adrenergic receptor antagonist propranolol during the escalation or maintenance of cocaine intake in a model of extended access (6 h) to cocaine self‐administration (0.5 mg/kg). The behavioural specificity of propranolol was tested using a non‐drug reward (saccharin). Daily administration of propranolol (15 mg/kg) prevented the development of escalation of cocaine self‐administration and partially reversed self‐administration after the establishment of escalation of intake. Moreover, propranolol dose‐dependently decreased the motivation for cocaine tested under a progressive ratio schedule of reinforcement during the development of escalation and after maintenance. Finally, propranolol administration had no effect on the escalation and maintenance of saccharin self‐administration. These results demonstrate that chronic treatment with propranolol provides therapeutic efficacy in reducing cocaine self‐administration during the development and after the establishment of escalation of cocaine self‐administration in an animal model relevant to cocaine use disorder. These results suggest that beta blockers should be further investigated as a target for medication development for the treatment of cocaine use disorder.