POSSIBILITY OF 5-HT3 RECEPTOR INVOLVEMENT IN ALCOHOL DEPENDENCE - A MICRODIALYSIS STUDY OF NUCLEUS-ACCUMBENS DOPAMINE AND SEROTONIN RELEASEIN RATS WITH CHRONIC ALCOHOL-CONSUMPTION
K. Yoshimoto et al., POSSIBILITY OF 5-HT3 RECEPTOR INVOLVEMENT IN ALCOHOL DEPENDENCE - A MICRODIALYSIS STUDY OF NUCLEUS-ACCUMBENS DOPAMINE AND SEROTONIN RELEASEIN RATS WITH CHRONIC ALCOHOL-CONSUMPTION, Alcoholism, clinical and experimental research, 20(9), 1996, pp. 311-319
The present study was performed to examine the involvement of serotoni
n-3 (5-HT3) receptors in the rat nucleus accumbens (ACC) in alcohol de
pendence. In alcohol-treated rats, perfusion of 40 mM K+ and 100 mM et
hanol (EtOH) through the microdialysis probe increased the extracellul
ar levels of ACC dopamine (DA), compared with controls. Perfusion of t
he serotonin (5-HT) uptake inhibitor sert-larine enhanced the extracel
lular levels of ACC 5-HT in both groups. Increased 5-HT availability i
n the synaptic clefts on the ACC further activated ACC DA release in t
he alcohol-treated rats, in comparison with controls. In the final exp
eriments, perfusion of the 5.0 mu M 5-HT3 receptor agonist 2-methyl-5-
HT (2-Me-5-HT) through the microdialysis probe enhanced the extracellu
lar levels of ACC DA. Magnitude of 2-Me-5-HT-induced DA release was si
gnificantly higher in alcohol-treated rats than in controls. On the ot
her hand, 40 mM K+- and 100 mM EtOH-induced extracellular 5-HT release
in alcohol-treated rats were markedly inhibited. These results show t
hat (1) chronic alcohol intake increases the sensitivity of 5-HT3 rece
ptors, (2) 5-HT3 receptors regulate DA release in the ACC, (3) the dop
aminergic neuronal systems associated with 5-HT3 ionophore in the ACC
were upregulated after chronic alcohol exposure, and (4) chronic alcoh
ol intake desensitizes the serotonergic neuronal systems in rat ACC. T
hese findings suggest that neurochemical functions of 5-HT3 receptors
in regulating DA release in the ACC after alcohol exposure compensate
for the dysfunction of serotonergic activity to restore the original p
roperties in processing alcohol tolerance and that the development of
alcohol dependence may be mediated by ACC 5-HT3 receptors.