Paulose,C S; Akash,George K; Anju, T R; Peeyush, K T(Journal of Biomedical Science(2008) 15:623–631, June 7, 2008)
[+]
[-]
Abstract:
Dopamine D2 receptors are involved in ethanol
self- administration behavior and also suggested to mediate
the onset and offset of ethanol drinking. In the present
study, we investigated dopamine (DA) content and Dopamine
D2 (DA D2) receptors in the hypothalamus and corpus
striatum of ethanol treated rats and aldehyde dehydrogenase
(ALDH) activity in the liver and plasma of ethanol
treated rats and in vitro hepatocyte cultures. Hypothalamic
and corpus striatal DA content decreased significantly
(P\0.05, P\0.001 respectively) and homovanillic acid/
dopamine (HVA/DA) ratio increased significantly
(P\0.001) in ethanol treated rats when compared to
control. Scatchard analysis of [3H] YM-09151-2 binding to
DA D2 receptors in hypothalamus showed a significant
increase (P\0.001) in Bmax without any change in Kd in
ethanol treated rats compared to control. The Kd of DA D2
receptors significantly decreased (P\0.05) in the corpus
striatum of ethanol treated rats when compared to control.
DA D2 receptor affinity in the hypothalamus and corpus
striatum of control and ethanol treated rats fitted to a single
site model with unity as Hill slope value. The in vitro
studies on hepatocyte cultures showed that 10-5 M and
10-7 M DA can reverse the increased ALDH activity in
10% ethanol treated cells to near control level. Sulpiride,
an antagonist of DA D2, reversed the effect of dopamine on
10% ethanol induced ALDH activity in hepatocytes. Our
results showed a decreased dopamine concentration with
enhanced DA D2 receptors in the hypothalamus and corpus
striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and
in vitro hepatocyte cultures with 10% ethanol as a compensatory
mechanism for increased aldehyde production
due to increased dopamine metabolism. A decrease in
dopamine concentration in major brain regions is coupled
with an increase in ALDH activity in liver and plasma,
which contributes to the tendency for alcoholism. Since the
administration of 10-5 M and 10-7 M DA can reverse the
increased ALDH activity in ethanol treated cells to near
control level, this has therapeutic application to correct
ethanol addicts from addiction due to allergic reaction
observed in aldehyde accumulation.