Effects of chronic ethanol administration on serotonin metabolism in the various regions of the rat brain (original) (raw)
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Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, 1996
Intraperitoneal injection 10 min before sacrifice of 1.5 g ethanol/kg weight produced an increase in rat striatal levels of homovanillic acid (HVA) (p < 0.05) but did not affect the striatal concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5HT) and 5-hydroxyindoleacetic acid (5-HIAA). A similar ethanol treatment led to decreases in 5-HT (p < 0.05) and 5-HIAA (p < 0.05) from cerebral cortex (prefrontal and anterior cingulate areas). The results point to several ethanol-linked alterations in central serotonergic and dopaminergic systems. COMP BIOCHEM PHYSIOL 113C, 399402, 1996.
Ethanol does not affect serotonin receptor binding in rodent brain
Alcohol, 1989
ALCOHOL 6(4) 277-280, 1989.-The effects of ethanol on serotonin (5-hydroxytryptamine, 5-HT) receptor binding in rat and mouse brain were determined under in vitro conditions and in mouse brain following seven days of ethanol ingestion. 5-HT~A receptor characteristics were measured utilizing the agonist [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]DPAT), and 5HT 2 receptorbinding studies utilized the antagonist [3H]ketanserin. At the highest concentration of ethanol tested in vitro (680 mM), there was only 25% inhibition of [3H]DPAT binding in rat and mouse brain and 14% inhibition of [3H]ketanserin binding in rat brain. Effects of an anesthetic concentration of ethanol (100 mM) on agonist binding in the presence and absence of the guanine nucleotide GTP were also evaluated in vitro in mouse brain. In no case did ethanol (100 mM) significantly affect 5-HT~A or 5-HT 2 receptor-binding characteristics. When 5-HT receptor characteristics were measured after mice consumed ethanol for seven days, there was no change in either 5-HT~A or 5-HT 2 receptor-binding properties in any of the brain areas examined.
Chronic Ethanol Administration Decreases 5-HT and Increases 5-HIAA Concentration in Rat Brain
Acta Pharmacologica et Toxicologica, 1980
The effect of acute and chronic ethanol administration on cerebral 5-hydroxytryptamine (5-HT) and 5hydroxyindoleacetic acid (5-HIAA) concentrations of male Sprague-Dawley and Wistar rats was studied. Acute ethanol administration caused a slight fall (by 13%) in 5-HT concentration and a slight increase (by 10%) in 5-HIAA concentration one hour after administration. In chronically treated rats the whole brain 5-HT concentration was decreased by 9% during ethanol intoxication. This fall was significant in the part of brain containing diencephalon, mesencephalon and telencephalon except cortex (by 23%; P<O.Ol) and in that containing pons and medulla oblongata (by 37%; P<O.OOI) but not in cerebral cortex. The cerebral 5-HIAA concentrations of chronically treated Wistar and Sprague-Dawley rats were increased during intoxication (4-6 hrs after last ethanol administration) and even more during withdrawal (16-18 hrs after last ethanol administration, by 24-58%; P<O.O5-0.01). The increase was observed in all three parts into which the brain of Wistar rats were dissected. Because ethanol did not further increase the probenecid induced elevation of cerebral 5-HIAA concentration, our results suggest that ethanol increases the cerebral 5-HIAA concentration by attenuating its removal from the brain.
Alcohol and Alcoholism, 2003
Aims: The influence of alcohol on the brain serotonergic system has been studied for several decades with some discordant results. The effects of continuous and constant treatment with ethanol on the rates of serotonin [5-hydroxytryptamine (5-HT)] synthesis in discrete regions of the rat brain were studied. Methods: 5-HT synthesis rates were measured using the α-[ 14 C]methyl-Ltryptophan autoradiographic method. The rats in the experimental group were treated with 50% ethyl alcohol and those in the control group received distilled water. The fluid was delivered subcutaneously by implanted osmotic mini-pumps for 14 days at the rate of 5 µl/h or 0.12 ml/day (0.06 ml of alcohol per day). Results: Chronic ethanol treatment, as delivered in the present experiment, induced a significant increase in the rate of 5-HT synthesis in descending serotonergic cell bodies (raphe pallidum, raphe obscurus, raphe magnus), nigrostriatal structures, the hippocampus and cortices. No significant changes were observed in the dorsal and median raphe nuclei or pineal body. The results suggest that there may be differences in the regulation of 5-HT synthesis in different brain structures after 14 days of continuous (subcutaneous) injection of 50% alcohol. Conclusions: Chronic ethanol treatments using osmotic mini-pumps induce non-uniform increases in 5-HT synthesis in the rat brain.
Pakistan journal of pharmaceutical sciences, 2015
Present study aims to depict the role of serotonergic pathways in discrete brain areas (hypothalamus, amygdala, and hippocampus) and their interaction with hypothalamic pituitary adrenal (HPA) axis in alcohol dependence and subsequent withdrawal syndrome in rats. Albino Wistar rats were fed a liquid diet containing alcohol for 4 weeks. Matched control rats were fed isocaloric amounts of the alcohol-free liquid diet, in which the alcohol contribution was substituted with maltose-dextrin. Brain regional tryptophan, 5-hydroxytryptamine (5-HT), 5-Hydroxyindoleacetic acid (5-HIAA) concentrations were determined using high performance liquid chromatography with flourimetric detector. Serum corticosterone was determined spectrofluorimetrically. Data analysis showed that there was significant increase in tryptophan (hippocampus), 5-HT (hippocampus and amygdala) and 5-HT turnover in all the three regions examined when alcohol administered rats were compared with matched controls. In contrast...
Acute and chronic actions of ethanol on CA1 hippocampal responses to serotonin
Brain Research, 1996
The effects of acute or chronic ethanol on serotonin (5-HT)-induced membrane hyperpolarization and inhibition of the slow Ca2+-dependent after hyperpolarization (sAHP) were recorded in rat CA1 pyramidal neurons in hippocampal slices using sharp intracellular electrodes. 5-HT (1-100 txM) caused concentration-dependent hyperpolarization of the membrane that was not altered by simultaneous 30 mM ethanol treatment, but blunted by 10 ixM buspirone, a weak 5-HT1A agonist. 5-HT (1-30 I-~M) also partially inhibited (~ 40%) the sAHP following a burst of five or more action potentials. Initially ethanol (30 raM) alone did not alter the sAHP, but over a period of 38 min, a slow increase in amplitude (~ 40%) was observed. 5-HT-mediated inhibition of the sAHP was significantly greater with ethanol present, regardless of the length of exposure. Pyramidal neurons in hippocampal slices prepared from ethanol-dependent animals showed no obvious signs of withdrawal related hyperexcitability and neither concentration-dependent membrane hyperpolarization nor sAHP inhibition caused by 5-HT were significantly changed from responses in controls. These results suggest that hyperpolarizing responses to 5-HT in hippocampal CA1 pyramidal neurons are functionally resistant to acute or chronic ethanol treatment. 5-HT-mediated inhibition of the sAHP is enhanced by ethanol acutely, but does not show an adaptive change as a result of ethanol dependence.
Reduced Serotonergic Immunoreactive Fibers in the Forebrain of Alcohol-Preferring Rats
Alcoholism: Clinical and Experimental Research, 1994
Our previous study indicated that 5-hydroxytryptamine (5-HT) immunoreactive fiber densities were decreased in specific areas of the brain in alcohol-preferring rats (P) when compared with alcoholnonpreferring rats (NP). The results of our current study show that there are quantitative and qualitative differences in 5-HT innervation in other selected regions of the forebrains of P rats. The 5-HT fiber density in the brains of young adult P and NP rats was measured by immunocytochemistry and quantitative image analysis. A routine error of two-dimensional quantitation of nerve fiber was addressed and an adjustment was made. The amount of 5-HT fibers was significantly lower in CA4 and fasciola cinereum of the dorsal hippocampus, caudate-putamen, and hypothalamus of the P as compared with NP rats (unpaired Student's t tests).
Drug and Alcohol Dependence, 1988
Male rats were treated with one ethanol (2.0 g/kg i.p.) or saline injections once a week for 50 weeks. During this treatment period the rats had in addition access to ethanol (10% in drinking fluid) as a choice against water for 24 h prior to the injection. During the following evaluation period, animals had a continuous choice between ethanol and water and the concentration of the ethanol solution increased every 3rd week from 5 to 10, 15 and 25%, with 10% as a reference tested between the other concentrations. The animals were killed after an abstinence of 4 weeks, whereupon the concentrations of noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were determined in the frontal cortex. In the remaining cerebral cortex, activity of monoamine oxidase, reuptake of NA and stimulated inositol phospholipid (PI) breakdown was also determined. Muscarinic binding sites were determined in the striatum. During treatment, saline injected rats had a constant voluntary 24 h ethanol intake. There was a decrease in the corresponding intake in the animals given the ethanol injections. The diminishing of the intake was more marked in rats starting treatment at an age of 19.4 weeks when compared to rats starting at an age of 5.4 weeks. In the evaluation period the ethanol intake was fairly constant for all groups. However, the regressions between intake of the reference concentration when plotted against the different tested concentrations were most marked in the group where ethanol injections started at an early age. In the total material there were significant F-values when concentrations of NA, 5-HIAA, 5-HT/5-HIAA in the cortex and muscarinic binding sites in the striatum were tested. Age could not be excluded as a contributing factor, but for muscarinic binding sites in the striatum, concentrations of DA and 5-HIAA in the cortex, and potassium stimulated PI breakdown in the cortex significant regressions with voluntary ethanol intake as dependent variable could be established. Since these intakes are stable, a causal relation with dependence may be involved.
Effect of ethanol on extracellular 5-hydroxytryptamine output in rat frontal cortex
European Journal of Pharmacology: Environmental Toxicology and Pharmacology, 1994
The effect of acute administration of ethanol on the release of 5-hydroxytryptamine (5-HT) in the frontal cortex of "Sardinian alcohol preferring" rats, "Sardinian non-preferring" rats and control rats was investigated using in vivo microdialysis. At the dosage of 2.5 g/kg i.p. ethanol increased the level of 5-HT in the dialysate by approximately 80 + 20% of basal values in the Sardinian alcohol preferring rats whereas no effect was observed in Sardinian non-preferring and control rats.