Effects of hypnotic drugs on methamphetamine-related behaviors: an ethological and molecular study in rodents and non-human primates

Abstract

Drug addiction is a chronic relapsing disorder which currently represents a global public health concern. Despite decades of research, there is no cure for drug abuse to date, mainly due to the heterogeneity of this disease and all the factors influencing it. Among them, one of the major clinical complaints reported by drug users is sleep impairment, which per se can worsen the course of drug abuse. Together with the nocturnal pattern of use of psychostimulants, these considerations pose sleep as an important factor in drug addiction, with sleep interventions possibly playing a critical role in the prevention and treatment of substance use disorders. In this scenario, we propose in the present study the investigation of the effects of temazepam and eszopiclone, two clinically approved hypnotic drugs from distinct classes, on methamphetamine-related behaviors. We will first investigate if both hypnotic drugs are equally effective in promoting sleep disrupted by methamphetamine in rhesus macaques. Then, through behavioral and in vivo microdialysis studies in mice and rhesus macaques, we will investigate if sleep promotion can affect the maintenance, extinction and reinstatement of the behavioral effects of methamphetamine. We aim to shed light on the mechanisms underlying the relationship between sleep and psychostimulant addiction, possibly providing relevant insights to clinical practices in rehabilitation and addiction prevention strategies.