Decreased dopamine D(2) receptor function in cerebral cortex and brain stem: their role in hepatic ALDH regulation in ethanol treated rats.
Ethanol exerts numerous pharmacological effects through its interaction with various neurotransmitters. The dopaminergic pathway is associated with cognitive, endocrine, and motor functions, and reinforcement of addictive substances or behaviours. Aldehyde dehydrogenase (ALDH) is a vital enzyme involved with alcohol metabolism and detoxification. In the present study, we investigated the role of cerebral cortex and brain stem dopamine D(2) receptors in the functional regulation on ALDH enzyme activity, in ethanol administrated rats. Two groups of rats were selected viz. control and alcoholic. Cerebral cortex, brain stem and the liver dopamine content was decreased significantly (P < 0.05, 0.05, 0.001, respectively) and homovanillic acid/dopamine (HVA/DA) ratio has significantly increased (P < 0.05, 0.001 and 0.001), respectively in ethanol treated rats when compared to control. Scatchard analysis of [(3)H]YM-09151-2 binding to synaptic membrane preparations of cerebral cortex and brain stem showed a significant decrease (P < 0.001, 0.05, respectively) in B (max) in ethanol treated rats compared to control and the K (d) also decreased significantly (P < 0.05). The ALDH analysis showed a significant increase (P < 0.05) in V (max) in cerebral cortex, plasma and liver of experimental rats when compared with control without having significant change in brain stem but with decreased K (m) (P < 0.001). Our results suggest that decreased function of dopamine mediated through DA D(2) receptor in the cerebral cortex and brain stem enhanced the brain, plasma and liver ALDH activity in ethanol treated rats. This ALDH regulation has significance to correct alcoholics from addiction due to allergic reaction observed in aldehyde accumulation.
George
Akash K
AK
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, 682022 Kerala, India.
Balarama Kaimal
S
S
Paulose
C S
CS
D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism / Q000502:physiology*
D017448:Receptors, Dopamine D2; D000431:Ethanol; D000444:Aldehyde Dehydrogenase