Effects of Orexin/Hypocretin on Ventral Tegmental Area Dopamine Neurons: An Emerging Role in Addiction

Abstract

(from the chapter) Addiction poses a significant threat to the health, social, and economic fabric of families, communities, and nations. The extent of worldwide psychoactive drug use is estimated at 2 billion alcohol users, 1.3 billion smokers, and 185 million drug users (UNDCP Statistics, 2002). Currently, there is no effective treatment for craving related to substance abuse. Several medications used clinically to counteract the effects of craving and relapse targeting different receptors have so far shown little efficacy. For example, drug-free retention rates with the use of opioid receptor antagonist, naltrexone, is often less that 20% in heroin addicts and 30-40% in alcoholics. Tricyclic antidepressants and serotonin reuptake inhibitors have been widely used in the treatment of cocaine addicts, but have not been efficacious. Finally, trials using the GABAB receptor agonist, baclofen, have shown reductions in cocaine craving, but long-term outcome studies looking at craving and continued cocaine use are needed. Taken together, novel targets are needed for the development of new medications for chronically relapsing forms of addiction. Interestingly, patients with narcolepsy are often treated with highly addictive amphetamine-like drugs such as methylphenidate, amphetamine, and -hydroxybutyrate, but they rarely become addicted to these drugs. Because narcolepsy results from a deficient orexin/hypocretin (ox/hcrt) system, the absence of addiction in narcoleptic patients treated with psychostimulants suggests the possibility of this system's involvement in the reinforcing aspect of addictive drugs. This chapter will discuss evidence for the interaction of these peptides in the neural circuits mediating drug-seeking behaviors. (PsycINFO Database Record (c) 2012 APA, all rights reserved).