The effect of ethanol consumption on dopamine and ethanol concentrations in the nucleus accumbens during the development of reinforcement and the involvement of the k-Opioid receptor in the modulation of dopamine activity during ethanol self-administration
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Abstract
A key process associated with the development of reinforcement is the release of
dopamine in the nucleus accumbens from mesolimbic cells of the ventral
tegmental area. There is evidence that accumbal dopamine activity increases
during operant ethanol self-administration, but it is unknown whether this effect is
related to appetitive or consummatory aspects of behavior. Neuroadaptations in
the mesolimbic system during the development of ethanol reinforcement are also
unclear. Studies were undertaken to address these issues, all of which
measured dopamine and ethanol concentrations in the nucleus accumbens of
rats using a procedure in which a fixed number of operant responses was
followed by 20 min of ethanol availability. An initial exposure to 5 or 10% ethanol
(with sucrose) resulted in reduced intake levels compared to controls and no
alterations in dopamine concentrations during consumption. In contrast, during
limited self-administration (about 7 days) of 10% ethanol (with sucrose) or long
term self-administration (over 40 days) of 10% ethanol, a brief rise in dopamine
levels occurred within 5 min of access that corresponded to consumption. During
the period in which the dopamine response occurred, brain ethanol
concentrations were low but increased progressively thereafter, indicating a rapid
dissociation between the two time courses. Together these results suggest that
the dopamine response was due to factors other than the pharmacological
properties of ethanol, such as the stimulus cues of the solution during acquisition.
These data also suggest that a dopamine response to ethanol occurs after the
development of motivated ethanol drinking. Furthermore, accumbal dopamine
activity during ethanol self-administration may be under the regulation of the
endogenous κ-opioid system, acting to suppress dopamine activity and ethanol
intake. We tested this hypothesis by blocking the κ-opioid receptor with nor
binaltorphimine during ethanol self-administration. Nor-binaltorphimine treatment
resulted in a brief increase in dopamine concentration 20 min after ethanol
drinking commenced. The latent rise in dopamine levels correlated positively
with accumbal ethanol concentration, suggesting that kappa blockade uncovered
a pharmacological stimulation of dopamine activity by ethanol.