Decreased dopamine D2 receptor function in cerebral cortex and brain stem: their role in hepatic ALDH regulation in ethanol treated rats

Abstract

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.

Correlating blood-based DNA methylation markers and prostate cancer risk in African-American men

“…In our logistic regression analysis tobacco smoke and alcohol use were significantly associated with aberrant methylation of RARβ 2, SPARC , LINE 1 and DRD 2 loci in AA patients with PCa suggesting that methylation of these genes could be associated with increased risk of PCa in patients who smoke tobacco and or consume alcohol. There are numerous reports to show that alcohol action is directly associated with neurotransmitters such as dopamine and serotonin and its receptors [ 48 , 49 ]. Our present observation of aberrant methylation in the DRD 2 gene and alcohol and/or tobacco use in blood samples from AA patients with PCa indicates that the status of DRD 2 methylation is correlated with lifestyle factors such as alcohol consumption and tobacco smoke in addition to serum vitamin D (discussed above) in AA PCa patients.…”

Homocysteine, Alcoholism, and Its Potential Epigenetic Mechanism

“…It alters their membranes as well as their ion channels, enzymes, N ‐methyl‐ d ‐aspartate (NMDA), and gamma‐aminobutyric acid (GABA) receptors. There are numerous reports showed EtOH action is directly associated with neurotransmitters such as dopamine, serotonin, GABA, NMDA, and its receptors (Benjamin et al., ; Fernando, ; George et al., , , ; McClintick et al., ; Spencer et al., ). Primary mechanism by which EtOH affects the brain is through regulation of neurotransmitters and ligands, voltage‐gated channels that are essential for neuronal excitability and synaptic function (Hoffman, ).…”

Enhanced 5-HT2A Receptor Status in the Hypothalamus and Corpus Striatum of Ethanol-Treated Rats

“…The functional regulation of the central GABA and 5-HT 2 receptors during liver regeneration (Sudha and Paulose 1998;Biju et al 2001Biju et al , 2002Pyroja et al 2007), decreased alpha1-adrenergic receptor binding in the cerebral cortex and brain stem during pancreatic regeneration (Ani et al 2006) and decreased dopamine D 2 receptor binding in the hypothalamus and brain stem of streptozotocindiabetic rats (Shankar et al 2007) were reported form our lab. The cerebral cortex and brainstem DA D 2 functional regulation contributed to the central nervous system manifestations in ethanol-treated rats is also reported (George et al 2007). Ethanol exposure alters the function of neurotransmitter receptors.…”