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Biomedical subjects

C Gianoulakis

Publications and source records attributed to C Gianoulakis.

At least 37 records · Page 2Linked to original sources
PubMed1995

Distribution of the mu and delta opioid binding sites in the brain of the alcohol-preferring AA and alcohol-avoiding ANA lines of rats.

There is experimental evidence indicating that the positive reinforcing effects of ethanol, responsible for voluntary ethanol consumption, are in part mediated by the endogenous opioid system. Differences in some components of the endogenous opioid system have been observed between lines and strains of animals bred selectively for their high or low ethanol consumption. Our objective was to investigate the presence of differences in the density and distribution of mu and delta opioid receptors in the brain of the alcohol-preferring Alko-Alcohol and alcohol-avoiding Alko, NonAlcohol lines of rats using iodinated ligands specific for mu ([D-Ala2, MePhe4, Met(o)ol5]-Enkephalin (FK 33-824)) or for delta ([D-Ser2]-leucine enkephalin-Thr) opioid receptors. Results calculated from studies on membrane preparations of whole brain minus cerebellum indicated that the Bmax and Kd were similar between the two lines of rats; however, autoradiographic studies showed that the alko-alcohol rats presented significantly higher density of mu opioid receptors in some brain regions, including nuclei of the limbic system that are important in mediating the reinforcing properties of many drugs of abuse. Furthermore, studies on brain membrane preparations indicated that both lines of rats were deficient in high affinity delta binding sites compared to Sprague-Dawley rats. Indeed, autoradiographic studies confirmed the presence of low density of the high affinity binding sites for [D-Ser2]-leucine enkephalin-Thr in both lines of rats. However, the density of the high affinity delta binding sites was higher in some distinct brain regions of the Alko-Alcohol than Alko-NonAlcohol rats. These differences in the density of both mu and delta opioid receptors may be partially responsible for the differences in voluntary ethanol consumption exhibited by these two lines of rats.

Alcoholism↗
PubMed1994

Enhanced activity of the brain beta-endorphin system by free-choice ethanol drinking in C57BL/6 but not DBA/2 mice.

The objective of the present studies was to investigate the effect of voluntary ethanol consumption for 21 days on the brain beta-endorphin system of C57BL/6 (alcohol-preferring) and DBA/2 (alcohol-avoiding) strains of mice. As expected, C57BL/6 mice consumed a significantly higher quantity of the 10% ethanol solution than the DBA/2 mice. Under basal conditions the content of beta-endorphin like peptides differed only in the nucleus accumbens, higher levels being found in the DBA/2 mice. Voluntary ethanol consumption induced an increase in the hypothalamic content of mRNA coding for proopiomelanocortin, associated with a significant increase in the tissue content of beta-endorphin-like peptides in the arcuate nucleus and septum of the C57BL/6 mice, but did not alter the activity of the brain beta-endorphin system of the DBA/2 mice. Since voluntary ethanol consumption was not associated with nutritional deficits and stress, the ethanol-induced enhanced activity of the brain beta-endorphin system of the C57BL/6 mice must be a direct effect of ethanol and may be important in controlling the voluntary ethanol consumption by this strain of mice.

Alcohol Drinking↗
PubMed1994

Genetics of alcoholism: role of the endogenous opioid system.

At the present time alcoholism is recognized as a metabolic disease exhibiting the clinical features of craving for alcohol, loss of control over drinking, tolerance and physical dependence on alcohol, while both epidemiological and experimental studies have demonstrated that genetic factors may be important in determining whether an individual has a high or low vulnerability to develop alcoholism. Evidence also indicates that alcoholism is not characterized by a single gene single allele inheritance. Instead it seems that multiple genes and environmental factors interact to increase or decrease an individual's vulnerability to become an alcoholic. Current research is aimed at investigating whether certain behavioral, physiological and biochemical markers are highly associated with the incidence of alcoholism. Among the biochemical markers currently under investigation is the endogenous opioid system and its implication in mediating the reinforcing effects of ethanol. It is the objective of this manuscript to review current research on: (a) the interactions of ethanol with the endogenous opioid system at the molecular level; (b) the existence of genetically determined differences in the response of the endogenous opioid system to ethanol between subjects at high and low risk for excessive ethanol consumption, as well as between lines of animals showing preference or aversion for ethanol solutions; (c) the decrease of alcohol consumption following pretreatment with opioid antagonists; and (d) the possible use of specific opioid receptor antagonists together with behavioral therapy to modify drinking behavior, to control craving and to prevent relapse.

Alcohol Drinking↗
PubMed1994

Spontaneous and ethanol-stimulated in vitro release of beta-endorphin by the hypothalamus of AA and ANA rats.

Previous studies demonstrated that both the spontaneous and ethanol-stimulated release of beta-endorphin (beta-EP) like-peptides (beta-EPLPs) by the hypothalami of the ethanol-preferring C57BL/6 mice is more pronounced than by the hypothalami of the ethanol-avoiding DBA/2 mice. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the in vitro release of beta-EP peptides by the hypothalami of the ethanol-preferring Alko-Alcohol (AA) and ethanol-avoiding Alko Non-Alcohol (ANA) lines of rats. Results indicated that although the spontaneous release of hypothalamic beta-EPLPs was higher by the ANA than by the AA rats, the percentage increase following exposure to various concentrations of ethanol was similar in both lines of rats. Furthermore, the release of hypothalamic beta-EPLPs following exposure to 30 mM ethanol was significantly higher than the release following exposure to 10 mM ethanol in the AA, but not the ANA, rats. Analysis of the released beta-EPLPs with Sephadex G-75 and reversed phase HPLC indicated that the nonacetylated beta-EP 1-31 was the major component in the hypothalamic perifusates of the AA rats, whereas the shorter and acetylated forms of beta-EP were the predominant components in the hypothalamic perifusates of the ANA rats. Because the shorter and acetylated forms of beta-EP are devoid of opioid activity, their pronounced release by the hypothalami of the ANA rats may be important in maintaining their low ethanol consumption, even after long-term access to ethanol solutions.

Alcohol Drinking↗
PubMed1994

Increased plasma atrial natriuretic peptide after acute injection of alcohol in rats.

A number of mechanisms may be involved in the protective effect of low ethanol (ETOH) consumption on the development of the age-dependent hypertension in both human and experimental animals. It was the objective of the present study to test the hypothesis that acute administration of low doses of ETOH would increase the plasma content of atrial natriuretic peptide (ANP), a hormone known to decrease blood pressure. Plasma ANP levels were increased significantly within 15 min after the i.p. injection of 1 or 2 g of ETOH/kg b.wt. The increase in plasma ANP was more pronounced and longer lasting after the i.p. injection of 2 rather than 1 g of ETOH/kg b.wt. This increase in plasma ANP level was associated with a rapid decrease of atrial ANP, but not of ventricular ANP which on the contrary was significantly elevated at 120 min postinjection. It has been suggested that opioids could play a significant role in controlling ANP release. In fact, circulating levels of beta-endorphin were also rapidly increased after the ETOH injection, with a time-course pattern similar to that of ANP. Furthermore, a highly positive correlation was found between the ETOH-induced changes of plasma ANP and beta-endorphin contents. Significant increases in plasma corticosterone and adrenocorticotropic hormone, but not aldosterone contents, were observed after the i.p. injection of 2 g of ETOH/kg b.wt., whereas plasma arginine vasopressin levels were significantly decreased at 15 but not at 120 min postethanol. There was no significant elevation in blood pressure during the 120-min experimental period, although a small tachycardia did develop in the ETOH-treated animals. Thus, acute in vivo administration of ETOH increased plasma ANP content in a dose-dependent manner and may play a role in the "protective" effect of low ETOH consumption in the development of the age-dependent hypertension.

Adrenocorticotropic Hormone↗
PubMed1993

Chronic ethanol increases proopiomelanocortin gene expression in the rat hypothalamus.

The effect of chronic ethanol exposure on proopiomelanocortin (POMC) mRNA accumulation, beta-endorphin (beta-EP) levels as well as incorporation of [3H]-phenylalanine into beta-EP-related peptides was investigated in the rat hypothalamus. Animals were treated with an ethanol-containing liquid diet for 15 days. Both sucrose pair-fed and ad libitum-fed control groups were included. The levels of immunoreactive beta-EP, as well as the relative proportions of nonacetyl and acetyl forms of beta-EP in the hypothalami of the ethanol-treated rats were not significantly different from those in the sucrose and lab chow fed control rats. Northern blot analysis of total hypothalamic RNA indicated that ethanol-treated rats had higher POMC mRNA levels than sucrose pair-fed and control rats. Quantitation of the in vitro incorporation of [3H]-phenylalanine into POMC, beta-lipotropin and beta-EP by the hypothalamus, using immunoprecipitation and polyacrylamide disc-gel electrophoresis with sodium dodecyl sulfate, revealed that the increased hypothalamic POMC mRNA content was associated with increased incorporation of [3H]-phenylalanine into POMC by the hypothalami of the ethanol-treated rats. It is concluded that chronic ethanol can alter the expression of the POMC gene in the hypothalamus.

Animals↗
PubMed1993

Effects of single and repeated exposures to ethanol on hypothalamic beta-endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice.

Ethanol has been shown to enhance the in vitro release of hypothalamic beta-endorphin (beta-EP). In the present study, the pattern of beta-EP release by the hypothalamus of two strains of mice, bred selectively for their preference (C57BL/6) or aversion (DBA/2) to ethanol, was investigated using a tissue perifusion system. The tissues were perifused with 20 mM ethanol for 30 min and the immunoreactive beta-EP content was estimated in perifusates collected every 2 min. Ethanol induced an enhanced release of hypothalamic beta-EP characterized by an initial spike followed by a gradual decrease toward baseline levels in both strains of mice. The ethanol-induced increase in beta-EP release by the hypothalamus of the C57BL/6 mice was more pronounced and longer lasting than that by the hypothalamus of the DBA/2 mice. Similar to beta-EP, an immediate sharp increase of corticotropin-releasing hormone (CRH) release was induced by ethanol which, however, did not present a spike but was maintained significantly higher than spontaneous release for the duration of ethanol exposure. Both ethanol-induced beta-EP and CRH release returned to basal levels within 10 min following removal of ethanol. That beta-EP levels did not remain elevated for the duration of ethanol exposure was not due to tissue depletion of releasable beta-EP pool, since exposure of the hypothalami to 10(-8) M CRH for 10 min, immediately after the perifusion with 20 mM ethanol, resulted in a large increase of beta-EP release. A second ethanol exposure 30 min after the first one did not induce an increase in beta-EP release. However, when the recovery period from the first ethanol exposure was extended to 60 min, a significant increase in the release of hypothalamic beta-EP was observed from the hypothalamus of the C57BL/6 but not of the DBA/2 mice. It is concluded that hypothalamic endorphinergic neurons present a fast, transient increase of beta-EP release in the presence of 20 mM ethanol, and become insensitive to subsequent ethanol exposures for a period of about 60 min. In addition, genetically determined differences exist with regards to the magnitude and duration of the ethanol-stimulated release of beta-EP, as well as on the length of the ethanol nonresponsive period. These differences may explain in part the differences in the voluntary ethanol consumption exhibited by these strains of mice.

Animals↗
PubMed1993

Endogenous opioids and excessive alcohol consumption.

Alcohol is one of the most popular drugs of abuse in our society, and alcoholism is an important cause of absenteeism at work and a major health and social problem. Ethanol induces a number of effects, such as disinhibition, a feeling of general well-being, tolerance and physical dependence. Since there are no specific receptors with which ethanol interacts, it has been proposed that ethanol exerts its effects by altering the activity of a number of neuronal and neuroendocrine systems. Studies have indicated that alcohol influences the activity of the dopaminergic, serotonergic and opioidergic systems. The implication of the endogenous opioid system in mediating some of the effects of ethanol is indicated by the observations that some of the behavioral and pharmacological effects of ethanol are similar to those of the opiates. Indeed, injections of small amounts of morphine increased ethanol consumption, while the administration of naltrexone decreased ethanol consumption among rats and other experimental animals, in a number of experimental paradigms, suggesting that endogenous opioids may play an important role in controlling voluntary ethanol consumption. This paper reviews studies of the effects of ethanol on the activity of the endogenous opioid system and on the importance of endogenous opioids in controlling alcohol consumption.

Alcohol Drinking↗
PubMed1992

Differences in the brain and pituitary beta-endorphin system between the alcohol-preferring AA and alcohol-avoiding ANA rats.

The content of pro-opiomelanocortin (POMC) mRNA was determined in the hypothalamus, as well as in the anterior and intermediate lobes of the pituitary gland of the alcohol-preferring AA and alcohol-avoiding ANA rats under basal conditions. In addition the content of beta-endorphin-like immunoreactivity (beta-EPLIR) was measured in nine brain regions, the anterior and intermediate lobes of the pituitary gland and the serum. The content of beta-EPLIR was significantly higher in the septum and significantly lower in the amygdala, and periaqueductal gray matter of the AA rats, while there was no significant difference between the AA and ANA rats in the arcuate nucleus plus median eminence, nucleus accumbens, caudate, hippocampus, and cortex. HPLC analysis indicated no significant differences in the relative proportions of non-acetyl and acetyl forms of beta-endorphin peptides in the hypothalamus, distinct brain regions, and anterior and neurointermediate lobes of the pituitary gland, between the AA and ANA rats. The content of POMC mRNA but not of beta-EPLIR was significantly higher in the hypothalamus and neurointermediate lobe of the AA rats, while the content of both beta-EPLIR and POMC mRNA were significantly higher in the anterior pituitary of the AA than of the ANA rats. Thus, there are genetically determined differences in the pituitary and brain beta-endorphin system between the AA and ANA rats, which may be important in controlling the differences in the voluntary ethanol consumption exhibited by these animals.

Alcohol Drinking↗
PubMed1992

The alcohol-preferring C57BL/6 mice present an enhanced sensitivity of the hypothalamic beta-endorphin system to ethanol than the alcohol-avoiding DBA/2 mice.

One of the systems proposed to mediate the reinforcing effects of ethanol is the endogenous opioid system. The objective of the present studies was to investigate the effects of various concentrations of ethanol on the release of beta-endorphin (beta-EP) by the hypothalami of mice showing either high (C57BL/6) or low (DBA/2) voluntary ethanol consumption. Results indicated that the release of beta-EP, either under basal conditions or in the presence of ethanol, was higher from the hypothalami of the C57BL/6 than of the DBA/2 mice. After exposure to various concentrations of ethanol, it was observed that for both strains of mice, low concentrations of ethanol (10, 20 and 25 mM) induced a more pronounced increase in the release of hypothalamic beta-EP than high concentrations of ethanol (30 and 60 mM) leading to an inverse U-shaped dose-response curve. Maximum release for both strains of mice was obtained at 20 mM ethanol. High-performance liquid chromatography analysis indicated that beta-EP 1-31 in the nonacetyl, opiate active form was the major form of the beta-EP-sized peptides released by the hypothalami of both strains of mice. The tissue content of beta-EP-like peptides was similar in the hypothalami of both strains of mice; however, the content of pro-opiomelanocortin mRNA was significantly higher in the hypothalami of the C57BL/6 mice. These genetically determined differences in the basal activity and in the response of the hypothalamic beta-EP system to ethanol may be partially responsible for the different ethanol consumption exhibited by these two strains of mice.

Alcohol Drinking↗
PubMed1990

Characterization of the effects of acute ethanol administration on the release of beta-endorphin peptides by the rat hypothalamus.

In the present studies the direct effect of ethanol on the release of beta-endorphin by the rat hypothalamus was investigated. When various concentrations of ethanol (10-120 mM) were added into the incubation medium, it was noticed that though low concentrations of ethanol (10, 20 and 30 mM) induced a pronounced increase in the release of beta-endorphin-like peptides from the hypothalamus, high concentrations of ethanol (40, 60 and 120 mM) induced a less pronounced increase. Exposure of hypothalamus to depolarizing concentrations of potassium chloride (following washing of the ethanol), provoked a significant release of beta-endorphin-like peptides, regardless of the ethanol concentration the tissues were exposed prior to the stimulation with the potassium chloride. Chromatographic analysis of the incubation media with Sephadex-G-75 revealed that the hypothalamus released mainly beta-endorphin-sized peptides. Analysis of the beta-endorphin-sized peptides with reverse-phase high performance liquid chromatography indicated the presence of beta-endorphin-(1-31) as well as non-acetyl and acetyl beta-endorphin-(1-27). Thus ethanol exerts a biphasic effect on the release of beta-endorphin-like peptides by the rat hypothalamus, with low concentrations inducing a dose-dependent increase, reaching maximum at 20 mM ethanol, and with higher concentrations of ethanol inducing a less pronounced increase in the release of beta-endorphin-like peptides, leading to an inverted U-shaped dose response relationship of ethanol and release of beta-endorphin-like peptides from the rat hypothalamus.

Animals↗
PubMed1990

Rats exposed prenatally to alcohol exhibit impairment in spatial navigation test.

Prenatal exposure to ethanol causes learning disabilities and low I.Q. scores. The objective of the present studies was to investigate whether exposure of rats to ethanol in utero, would induce a deficit in spatial memory in adult life. Pregnant rats were fed with an ethanol diet from day 1 of pregnancy till parturition. Control rats were either pair-fed with an isocaloric sucrose diet or were fed with lab-chow ad libitum. On the first day of birth, offspring exposed to ethanol in utero were placed with a control mother fed with lab-chow, while offspring of the lab-chow fed dams were placed with ethanol-treated dams. At 40, 60 and 90 days postnatally, behavioral testing was performed using the Morris swim maze, a test of spatial memory. Results indicated that the offspring exposed to ethanol in utero presented deficits in spatial memory processes. Ethanol did not completely block the learning of the swim maze task but the alcohol-exposed offspring exhibited longer latencies to perform the task, swam longer distances prior to locating and climbing onto the platform, and when the platform was removed, searched for it in all 4 quadrants of the pool. Restricted caloric intake during gestation and maternal behavior in early postnatal life also induced deficits in the performance on the swim maze task. However, these deficits were mild and short-lasting being absent at 60 and 90 days of age. In contrast, the deficits induced by ethanol were more severe and longer-lasting, being present in adult life.

Animals↗
PubMed1989

The effect of ethanol on the biosynthesis and regulation of opioid peptides.

Alcoholism and alcohol abuse are serious health problems. Alcohol is known to influence the activity of a number of biological systems, for example the hormonal and neuronal systems. One of the biological systems whose activity is greatly influenced by alcohol is the endogenous opiate system. Alcohol modifies the function of both opiate receptors and opioid peptides. In fact it has been proposed that many of the effects of ethanol are mediated by its effects on the endogenous opiate system. This review will present results from various laboratories on the effects of acute and chronic ethanol treatments on various species, and on the release, biosynthesis and post-translational processing of the endorphins, enkephalins and dynorphins, the three known families of endogenous opioid peptides. Furthermore, the effect of acute and chronic ethanol consumption on the beta-endorphin system in man, and the possible implications of the functional activity of the endogenous opiate system for the genetic predisposition to alcoholism will be discussed.

Alcoholism↗
PubMed1989

Different pituitary beta-endorphin and adrenal cortisol response to ethanol in individuals with high and low risk for future development of alcoholism.

The purpose of the present studies was to investigate the activity of the adrenal gland and the pituitary beta-endorphin system in individuals from families with a 3 generation history of alcoholism, High Risk group, or from families without history of alcoholism, Low Risk group. All subjects had a medical examination, a drinking behavior personal interview and the Michigan Alcoholism Screening Test. Individuals with medical problems or excessive drinking were not included in the study. On the day of testing, a blood sample was taken at 9:00 a.m., then the subject drank a placebo drink or an ethanol solution (0.5 g ethanol/kg B.Wt.). Additional blood samples were taken at 15, 45 and 120 minutes post-drink. Results indicated that individuals of the High Risk group had lower basal levels of beta-endorphin like immunoreactivity (beta-EPLIR) than individuals of the Low Risk group. The dose of 0.5 g ethanol/kg B.Wt. induced an increase in the plasma content of beta-EPLIR of the High Risk group, but not of the Low Risk group. In the Low Risk group ethanol did not induce an increase above the 9:00 a.m. levels, however, it attenuated the beta-endorphin decrease overtime, observed following the placebo drink. Analysis of beta-endorphin-like peptides in the plasma of the High Risk group, with Sephadex G-75 chromatography indicated that the major component of the plasma beta-EPLIR was beta-lipotropin. Plasma cortisol levels, following ethanol intake, presented a small increase in the High Risk group but not in the Low Risk group. Both groups presented similar blood alcohol levels. The basal levels of immunoreactive cortisol and beta-endorphin in the plasma of individuals who were alcoholics, but had been abstinent for at least six months prior to testing were similar to the levels of the High Risk group. Thus there are differences both in the basal levels and in the response of the cortisol and the pituitary beta-endorphin system to an acute ethanol challenge between the two groups.

Adult↗
PubMed1989

Prenatal exposure to ethanol alters the ontogeny of the beta-endorphin response to stress.

To determine whether prenatal exposure to ethanol alters the response of the beta-endorphin (beta-EP) system to stress, the effect of two types of stressful stimuli, ether and cold, was examined in the offspring of rats which during pregnancy were: (a) fed with an ethanol-containing diet; (b) pair-fed with an isocaloric sucrose diet; and (c) fed ad libitum with standard lab chow (basic control group). The effect of stress on the content of beta-EP in the serum, pituitary gland and hypothalamus, as well as on the serum corticosterone and hypothalamic corticotropin-releasing factor (CRF) content was examined. Pups prenatally exposed to ethanol had significantly higher serum beta-EP levels on Day 1 and higher serum corticosterone levels on Days 1-3 when compared to their pair-fed or basic controls. On all days tested pituitary beta-EP content was lower in the offspring of the ethanol-treated rats than in the control groups. There was no difference in the total hypothalamic beta-EP content between the three treatment groups; however, during the first 10 days of life a higher concentration (ng/mg protein) of beta-EP was observed in the hypothalami of the ethanol and the pair-fed group when compared to the basic control pups. Hypothalamic CRF levels, though significantly lower in the pups exposed to ethanol in utero than in the control groups on Day 3, increased significantly in the ethanol group between Days 14 and 22, while no significant change was observed during this period in either of the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ontogeny of the beta-endorphin response to stress in the rat: role of the pituitary and the hypothalamus.

Neonatal rats show a period of diminished adrenocorticotropin responsiveness to stress during the first 2 weeks of life. To test whether beta-endorphin-like peptides (beta-EPLPs) follow the same pattern of hyporesponsiveness to stress during this period, we examined the ontogeny of the beta-EPLPs response to two different types of stressors (ether vapors and cold) during the early postnatal period. The content of beta-EPLPs was estimated in the serum, the pituitary gland and the hypothalamus prior to and 5 min following exposure to stressful stimuli. Furthermore, to determine the relationship between the responsiveness of beta-EPLPs to stress and that of the hypothalamic-pituitary-adrenal axis in the developing rat, the content of hypothalamic corticotropin-releasing factor (CRF) and serum corticosterone was estimated prior to and following stress. Results indicated that stress induced an increase in the serum corticosterone levels at all ages tested (days 1-22), however, the stress-induced elevations of serum corticosterone were significantly greater on days 1 and 22 than on days 3-14. Significant stress-induced elevations of serum immunoreactive beta-endorphin (ir-beta-EP) were observed on days 14 and 22 of life, while changes on days 1, 3, 8 and 10 were either nonexistent or not statistically significant. Gel filtration analysis revealed that the increases in serum ir-beta-EP following stress on days 14 and 22 resulted primarily from increases in the beta-lipotropin component with lesser increases in the beta-endorphin component. Pituitary content of beta-EPLPs was not affected by stress before day 10, but was markedly reduced in the 10- and 14-day-old rats, following stress. A similar, although not statistically significant decrease was observed in the pituitary content of beta-EPLPs of the 22-day-old rats after exposure to stress. Furthermore, exposure to cold stress in the 14-day-old rats induced more pronounced changes in the serum ir-beta-EP and corticosterone levels as well as in the pituitary ir-beta-EP content than it did with ether stress. Despite variations in serum corticosterone as well as serum and pituitary content of beta-EPLPs, no changes in the hypothalamic ir-beta-EP content were seen in rats after subjection to stress, while small, not statistically significant reductions in the hypothalamic CRF content were observed at 5 min after the onset of stress in the 14-and 22-day-old rats. Thus, during the first 2 weeks of life neonatal rats exhibit a reduced capacity to secrete beta-EPLPs in response to stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗