A Neurochemical Basis for Alcohol and Other Drug Addiction

Abstract

There are major clinical observations in alcohol and other drug addicts and neurochemical studies in animals and humans that support the hypothesis for a common neurochemical basis for alcohol and other drug addiction. The common occurrence of concurrent alcohol and multiple drug dependence in clinical and general populations, family history and genetic studies, and basic and clinical research in the neurochemistry of addictive behavior provide evidence for a common genealogical vulnerability to combined alcohol and other drug addiction. Clinical neurochemical models for addictive behaviors can be derived from neurochemical pathways for the initiation and sustenance of addictive disorders. The role of tolerance and dependence is not specific to addiction but indicates a homeostatic response of the brain to the presence of a foreign substance. Animal and human studies are analyzed for clinical synthesis of a neurochemical basis for addictive disorders.

Regulation of the norepinephrine transporter by α‐synuclein‐mediated interactions with microtubules

“…Proper regulation of the norepinephrine transporter (NET) activity and trafficking is critical to functions of learning, memory, attention, affect, sleep and mood (Aston‐Jones et al. , 2000; Aston‐Jones & Cohen, 2005; Bonisch & Bruss, 2006), as well as pathology of several mental diseases and disorders of the nervous system (Jellinger, 1991; Miller & Gold, 1993; Klimek et al. , 1997; Gesi et al.…”

Regulated interactions of the norepineprhine transporter by the actin and microtubule cytoskeletons

“…Norepinephrine transporter plays a critical role in maintaining homeostasis of noradrenergic neurons. Its activity underlies arousal, attention, and sleep, and a variety of disorders, such as depression, attention deficit disorders, drug addiction and Parkinson’s disease (Jellinger 1991; Miller and Gold 1993; Klimek et al. 1997; Aston‐Jones et al.…”

“…Norepinephrine transporter plays a critical role in maintaining homeostasis of noradrenergic neurons. Its activity underlies arousal, attention, and sleep, and a variety of disorders, such as depression, attention deficit disorders, drug addiction and Parkinson's disease (Jellinger 1991;Miller and Gold 1993;Klimek et al 1997;Aston-Jones et al 2000;Gesi et al 2000;Zahniser and Doolen 2001;Marien et al 2004;Aston-Jones and Cohen 2005;Bonisch and Bruss 2006;Kim et al 2006). Many modes of regulating NET have been identified including transient activation of kinases and phosphatases Apparsundaram et al 2001;Holton et al 2005;Jayanthi et al 2004Jayanthi et al , 2006Sung and Blakely 2007;Yang and Raizada 1999) and chronic regulation via drugs (Benmansour et al 2004;Dipace et al 2007;Frazer 2001;Galli et al 1995;Hebert et al 2001;Heikkila et al 1975;Kantor et al 2004;Kitayama et al 2006;Mash et al 2005;Miller and Gold 1993;Pacholczyk et al 1991;Xu et al 2000;Zhu et al, 1998), yet a clear mechanism of regulation that is both longterm and endogenous remains elusive.…”

Training psychiatric residents in addiction

“…The vitally important clinical decision of treatment selection for the addict must be reevaluated in the light of ongoing research and consensus in the field (65). The biological underpinnings of addiction are better understood than ever (66,67) and must be grasped by the psychiatrist who hopes to prescribe effectively the medications described in this article. As the above-cited review articles emphasize, addiction treatment has entered the scientific realm, and should be practiced with an eye toward risk of treatment (and no treatment), data-based efficacy of treatment estimations, and cost analyses of treatment.…”