The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement.

Abstract:

:The neurobiological processes by which ethanol seeking and consumption are established and maintained are thought to involve areas of the brain that mediate motivated behavior, such as the mesolimbic dopamine system. The mesolimbic dopamine system is comprised of cells that originate in the ventral tegmental area (VTA) and project to several forebrain regions, including a prominent terminal area, the nucleus accumbens (NAcc). The NAcc has been subdivided into core and shell subregions. Both areas receive converging excitatory input from the cortex and amygdala and dopamine input from the VTA, with the accumbal medium spiny neuron situated to integrate the signals. Although forced ethanol administration enhances dopamine activity in the NAcc, conclusions regarding the role of mesolimbic dopamine in ethanol reinforcement cannot be made from these experiments. Behavioral experiments consistently show that pharmacological manipulations of the dopamine transmission in the NAcc alter responding for ethanol, although ethanol reinforcement is maintained after lesions of the accumbal dopamine system. Additionally, extracellular dopamine increases in the NAcc during operant self-administration of ethanol, which is consistent with a role of dopamine in ethanol reinforcement. Behavioral studies that distinguish appetitive responding from ethanol consumption show that dopamine is important in ethanol-seeking behavior, whereas neurochemical studies suggest that accumbal dopamine is also important during ethanol consumption before pharmacological effects occur. Cellular studies suggest that ethanol alters synaptic plasticity in the mesolimbic system, possibly through dopaminergic mechanisms, and this may underlie the development of ethanol reinforcement. Thus, anatomical, pharmacological, neurochemical, cellular, and behavioral studies are more clearly defining the role of mesolimbic dopamine in ethanol reinforcement.

journal_name

Pharmacol Ther

authors

Gonzales RA,Job MO,Doyon WM

doi

10.1016/j.pharmthera.2004.06.002

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

121-46

issue

2

eissn

0163-7258

issn

1879-016X

pii

S0163-7258(04)00095-6

journal_volume

103

pub_type

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