Volume 1121, Issue 1 p. 639-655

The Orbitofrontal Cortex, Impulsivity, and Addiction

Probing Orbitofrontal Dysfunction at the Neural, Neurochemical, and Molecular Level

CATHARINE A. WINSTANLEY

CATHARINE A. WINSTANLEY

University of British Columbia, Department of Psychology, Vancouver, BC, Canada

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First published: 18 December 2007
Citations: 79
Address for correspondence: Catharine A. Winstanley, Ph.D., University of British Columbia, Department of Psychology, 2136 West Mall, Vancouver BC, V6T 1Z4, Canada. Voice: (604) 822 3128; fax: (604) 822 6923.
[email protected]

Abstract

Abstract: The association between impulsivity and addiction is currently a topic of intense research interest. Investigations into the neurobiological basis of aspects of impulse control have revealed some striking parallels between the brain circuitry and neurochemical systems implicated in drug dependence and impulsive behavior. Both processes are heavily regulated by limbic corticostriatal circuits including the orbitofrontal cortex (OFC) and nucleus accumbens (NAC), and are modulated by dopamine (DA) and serotonin (5-HT). Hypoactivity within the OFC has been observed in recently abstinent cocaine users, and this is thought to contribute to the cognitive deficits associated with drug abuse, including impairments in impulse control. However, the neurobiological mechanisms underlying these functional and behavioral deficits are unclear. In parallel to observations made in the NAC, recent data indicate that chronic cocaine use also induces the transcription factor ΔFosB in the OFC and that this plays a role in the cognitive sequelae of chronic cocaine administration. In particular, ΔFosB appears to be involved in the development of tolerance to the disruptive effects of acute cocaine on impulsivity and motivation observed after repeated cocaine administration. Increased ΔFosB also contributes to increased impulsivity during withdrawal from the drug. Both effects could be attributed to the up-regulation of local inhibitory processes in the OFC after over-expression of ΔFosB and chronic cocaine treatment. Through integrating what is known of the interaction between addictive drugs and impulsivity at the neural, neurochemical, and molecular level, novel insight may be obtained into the multi-faceted regulation of the addicted state.