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Possibility of 5‐HT 3 Receptor Involvement in Alcohol Dependence: A Microdialysis Study of Nucleus Accumbens Dopamine and Serotonin Release in Rats with Chronic Alcohol Consumption
Author(s) -
Yoshimoto K.,
Yayama K.,
Sorimachi Y.,
Tani J.,
Ogata M.,
Nishimura A.,
Yoshida T.,
Ueda S.,
Komura S.
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01799.x
Subject(s) - nucleus accumbens , microdialysis , dopamine , serotonin , alcohol , alcohol dependence , chemistry , medicine , receptor , pharmacology , endocrinology , biochemistry
The present study was performed to examine the involvement of serotonin‐3 (5‐HT3) receptors in the rat nucleus accumbens (ACC) in alcohol dependence. In alcohol‐treated rats, perfusion of 40 mM K + and 100 mM ethanol (EtOH) through the microdialysis probe increased the extracellular levels of ACC dopamine (DA), compared with controls. Perfusion of the serotonin (5‐HT) uptake inhibitor sertlarine enhanced the extracellular levels of ACC 5‐HT in both groups. Increased 5‐HT availability in the synaptic clefts on the ACC further activated ACC DA release in the alcohol‐treated rats, in comparison with controls. In the final experiments, perfusion of the 5.0 μ M 5‐HT 3 receptor agonist 2‐methyl‐5‐HT (2‐Me‐5‐HT) through the microdialysis probe enhanced the extracellular levels of ACC DA. Magnitude of 2‐Me‐5‐HT‐induced DA release was significantly higher in alcohol‐treated rats than in controls. On the other hand, 40 mM K + ‐ and 100 mM EtOH‐induced extracellular 5‐HT release in alcohol‐treated rats were markedly inhibited. These results show that (1) chronic alcohol intake increases the sensitivity of 5‐HT 3 receptors, (2) 5‐HT 3 receptors regulate DA release in the ACC, (3) the dopaminergic neuronal systems associated with 5‐HT 3 ionophore in the ACC were upregulated after chronic alcohol exposure, and (4) chronic alcohol intake desensitizes the serotonergic neuronal systems in rat ACC. These findings suggest that neurochemical functions of 5‐HT 3 receptors in regulating DA release in the ACC after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance and that the development of alcohol dependence may be mediated by ACC 5‐HT 3 receptors.