Anti-relapse medications: Preclinical models for drug addiction treatment

Abstract

Addiction is a chronic relapsing brain disease and treatment of relapse to drug-seeking is considered the most challenging part of treating addictive disorders. Relapse can be modeled in laboratory animals using reinstatement paradigms, whereby behavioral responding for a drug is extinguished and then reinstated by different trigger factors, such as environmental cues or stress. In this review, we first describe currently used animal models of relapse, different relapse triggering factors, and the validity of this model to assess relapse in humans. We further summarize the growing body of pharmacological interventions that have shown some promise in treating relapse to psychostimulant addiction. Moreover, we present an overview on the drugs tested in cocaine or methamphetamine addicts and examine the overlap of existing preclinical and clinical data. Finally, based on recent advances in our understanding of the neurobiology of relapse and published preclinical data, we highlight the most promising areas for future antirelapse medication development.

Methamphetamine Self-Administration Causes Persistent Striatal Dopaminergic Alterations and Mitigates the Deficits Caused by a Subsequent Methamphetamine Exposure

“…Previous studies indicated that METH self-administration in rats provides a clinically relevant exposure pattern of human METH abuse (Yahyavi-Firouz-Abadi and See, 2009). Results of the current study extend these findings by revealing that METH self-administration decreases striatal DAT immunoreactivity and/or function.…”

Novel Cocaine Vaccine Linked to a Disrupted Adenovirus Gene Transfer Vector Blocks Cocaine Psychostimulant and Reinforcing Effects

“…The literature indicates that stress, drug-associated cues, and brief exposure to the drug itself can trigger drug craving and relapse to drug use in humans (Epstein et al, 2006;Yahyavi-Firouz-Abadi and See, 2009). Similarly, it is well established that animals that undergo extinction of drug self-administration reinstate responding when they are primed with a previously self-administered drug or other drugs of the same class (Stewart, 2000).…”

Chronic N-Acetylcysteine during Abstinence or Extinction after Cocaine Self-Administration Produces Enduring Reductions in Drug Seeking

“…Thus, the development of effective antirelapse medication is a critical goal of pharmacotherapy for addiction. Although a large number of pharmacological agents have been assessed in animal models of addiction and clinical studies (Yahyavi-Firouz-Abadi and See, 2009), there are no currently available drugs with established efficacy for the treatment of psychostimulant addiction and relapse.…”