Intranasal Oxytocin Reduces Cocaine Conditioned Locomotion and Anxiety‐like Behaviors due to a Cross‐talk with the Endocannabinoid System within the Mesolimbic System

Abstract

Oxytocin (OT) is a neuropeptide secreted by the hypothalamic paraventricular nucleus (PVN) and commonly associated with social behaviors, stress responses and drug‐addiction. Previous studies have shown that OT has anxiolytic properties associated with cues in a cocaine‐conditioning paradigm, but the underlying mechanism remains unknown. This study aims to characterize possible mechanistic interactions between OT and the endocannabinoid system mediating cocaine conditioning and anxiety response, in particular the cannabinoid receptor type 1 (CB1). Rats were exposed to activity chambers after receiving systemic intraperitoneal injections of cocaine (10 mg/kg) or saline 0.9%. during five consecutive days. On the testing session (D7), rats received intranasal infusions of OT (1 μg/μL) or vehicle (saline 0.9%) 30 minutes prior being exposed to the cue‐associated environment. Our results showed that OT pretreatment reduced both cocaine‐paired conditioned locomotion and anxiety‐like behaviors. Preliminary immunohistochemical analysis showed a colocalization of OT receptors and CB1 receptors within the nucleus accumbens (NAc) and the pre‐frontal cortex (PFC) in all treated animals. However, colocalization is pronounced when animals received intranasal OT pretreatment. The proposed mechanism includes a cross‐talk between OT and endocannabinoid system within mesolimbic system that might be responsible for the anxiety modulation triggered by cocaine exposure. This preliminary data suggests intranasal OT as a novel therapeutic approach of cocaine addiction.Support or Funding InformationNIH BP‐ENDURE Neuro‐ID Program ‐ University of Puerto Rico‐Rio Piedras Campus (1R25MH092912‐01); RCMI Program (G12 MD007600); Nikon A1 Confocal Microscope (NSF DBI‐1337284); Dr. Manuel Díaz and Dr. Amelia Merced, Institute of Neurobiology, University of Puerto Rico‐Medical Sciences Campus