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V G Erwin

Publications and source records attributed to V G Erwin.

At least 73 records · Page 4Linked to original sources
PubMed1987

Central mechanisms of ethanol-induced adrenocortical response in selectively bred lines of mice.

Selectively bred long-sleep (LS) and short-sleep (SS) mice differ markedly in ethanol-induced adrenocortical response. Intracerebroventricular injections of saline elicited a 'stress-induced' adrenocortical response in both lines of mice, and intracerebroventricular infusions of noradrenergic and cholinergic compounds modulated ethanol-induced and stress-induced adrenocortical responses differentially in these mice. Clonidine, an alpha 2-adrenergic agonist, blocked ethanol-induced elevations in plasma corticosterone in a dose-dependent manner (1 and 10 micrograms) in LS mice; however, only the 10-micrograms dose of clonidine effectively antagonized this response in SS mice. Clonidine was less effective in blocking adrenocortical activity induced by stress than that induced by ethanol. Yohimbine, an alpha 2-adrenergic antagonist, induced a marked elevation in plasma corticosterone in LS mice but not in SS mice; however, this compound did not alter ethanol-induced adrenocortical responses in either line of mice. Yohimbine reversed the inhibitory effect of clonidine in ethanol-treated LS and SS mice. Phentolamine, a nonspecific alpha-adrenergic antagonist, and propranolol, a beta-adrenergic antagonist at high doses (10 micrograms), produced slight increases in plasma corticosterone in LS mice only. Neither these compounds nor methoxamine, a nonspecific alpha-adrenergic agonist, altered the effect of ethanol on adrenocortical activity in LS or SS mice. Carbachol, a mixed muscarinic/nicotinic agonist, significantly increased adrenocortical response in both LS and SS mice and potentiated ethanol-induced elevation in plasma corticosterone in both lines of mice. However, atropine, a nonspecific muscarinic antagonist, or hexamethonium, a nicotinic antagonist, did not modify ethanol-induced elevations in plasma corticosterone in LS and SS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Deterrents↗
PubMed1987

Calcium influence on neurotensin and beta-endorphin enhancement of ethanol sensitivity in selectively bred mouse lines.

Intracerebroventricular (icv) administration of neurotensin produced a dose-dependent increase in ethanol sensitivity as measured by blood ethanol concentration at loss of righting reflex in SS/Ibg (SS) but not in LS/Ibg (LS) mice. Central administration of calcium also enhanced ethanol sensitivity of SS and to a lesser extent LS mice. Concurrent icv administration of calcium and neurotensin resulted in an additional enhancement of sensitivity to ethanol over that seen with either substance alone in both mouse lines. A dose-dependent increase in ethanol sensitivity was also produced in response to central administration of beta-endorphin in SS mice. No additional increase in sensitivity was noted following administration of beta-endorphin plus calcium. These results suggest a specific interaction of calcium and neurotensin may be involved in the mechanism through which ethanol elicits intoxication. The difference in response of LS and SS mice to neuropeptide and calcium-induced alterations in ethanol sensitivity may be related to the genetically selected differences to the acute narcotic actions of ethanol in these mice.

Alcoholic Intoxication↗
PubMed1986

Nicotine alters catecholamines and electrocortical activity in perfused mouse brain.

Nicotine differentially altered electrocortical (ECoG) activity and brain catecholamine metabolism in mice (C3H and C57BL) known to differ in behavioral response to nicotine. Nicotine appeared to produce a concentration dependent desynchronization to ECoG activity in isolated perfused mouse brain (IPMB) from C3H mice. Homovanillic acid (HVA) production was unchanged in C3H perfused brains while an apparent reduction in 3-methoxy-4-hydroxyphenethyleneglycol (MPHG) was observed. Brain content of norepinephrine and dopamine remained relatively constant in the various regions tested. In IPMB from C57BL mice, nicotine elicited an enhancement of ECoG amplitude which was accompanied by decreased HVA production rates. A downward trend in MHPG production was also observed. These effects were associated with increased levels of norepinephrine and dopamine in various brain regions.

Animals↗
PubMed1986

Calcium influence on neuronal sensitivity to ethanol in selectively bred mouse lines.

Sensitivity to ethanol, as measured by blood ethanol concentration at loss of righting reflex, was increased significantly in SS but not LS mice following intracerebroventricular (ICV) administration of calcium chloride or A23187, a calcium ionophore. Magnesium chloride or lanthanum chloride, ICV, did not alter sensitivity to ethanol in either SS or LS mice, further indicating a specificity for calcium cation. Calcium was without effect on sensitivity to halothane narcosis in LS or SS mice. Endogenous brain calcium content was similar in these mouse lines, and ethanol administration either in vivo or in vitro did not alter brain calcium concentration. These results indicate that differences in brain sensitivity to ethanol are mediated, in part, by genetic differences in calcium-related processes and support the hypothesis that ethanol-induced narcosis may be due to alterations in calcium metabolism in the CNS.

Animals↗
PubMed1986

Effects of 6-hydroxydopamine on brain catecholamines and on acute actions of ethanol in LS/Ibg and SS/Ibg mice.

LS/Ibg (LS) and SS/Ibg (SS) mice differ in ethanol-induced duration of loss of righting response or sleep time, hypothermia, hyperglycemia, and blood ethanol concentrations at regaining righting response. These differences in response to ethanol are a result of differences in central nervous system sensitivity and are mediated by polygenic systems. Studies have indicated that catecholaminergic systems may be involved in the differential effects of ethanol in LS and SS lines of mice (Masserano JM, Weiner N: Investigations into the neurochemical mechanisms mediating differences in ethanol sensitivity in two lines of mice. J Pharmacol Exp Ther 221:404-408, 1982). In this study the neurotoxin, 6-hydroxydopamine (6-OHDA), intracerebroventricular, was used to test this hypothesis. Administration of 6-OHDA markedly altered thermoregulation in LS mice but produced little effect in SS mice, and ethanol-induced hyperglycemia was attenuated in both LS and SS mice by 6-OHDA. Ethanol-induced sleep time was increased in SS mice pretreated with 100 micrograms of 6-OHDA, intracerebroventricular, whereas this response in LS mice was unaffected by 6-OHDA administration. Changes in sleep time were not related to changes in blood ethanol concentrations, indicating that 6-OHDA alters ethanol-induced sleep time by mechanisms other than brain sensitivity. Levels of norepinephrine and dopamine were determined in three brain regions, and the altered capacities for thermoregulation and glucoregulation were associated with changes in hypothalamic catecholamine levels.

Animals↗
PubMed1986

Ethanol-induced adrenomedullary catecholamine secretion in LS/Ibg and SS/Ibg mice.

Ethanol, administered i.p., produced a dose-dependent increase in plasma norepinephrine and epinephrine concentrations in LS/Ibg (LS) but not in SS/Ibg (SS) lines of mice. Ethanol-induced elevations of plasma epinephrine in LS mice were approximately 10-fold greater than those observed in SS mice. Plasma epinephrine and norepinephrine attained peak concentrations at 20-min post-ethanol administration at doses ranging from 2.8 to 4.1 g/kg. Plasma catecholamines remained elevated for approximately 1 hr and returned to basal values 2 hr after ethanol administration. Significant correlations were obtained between blood ethanol (r = 0.99), plasma epinephrine (r = 0.92) and plasma glucose (r = 0.98) as a function of ethanol dose in LS mice. Chlorisondamine (3 mg/kg), a ganglionic blocker, abolished completely the ethanol-induced increase in plasma catecholamines. These results confirm previous suggestions that the response is centrally mediated through an increased sympathetic outflow rather than by a direct effect on the adrenal medulla. The increase in plasma epinephrine and associated hyperglycemia produced by ethanol was not observed with pentobarbital or halothane anesthesia. Ethanol-induced hypothermia was diminished markedly (47%) by an elevated ambient temperature (28 degrees C) without reducing the hyperglycemic response to ethanol. These results suggest that ethanol-induced hypothermia does not mediate ethanol-induced adrenomedullary catecholamine secretion and concomitant hyperglycemia. It is proposed that the differential ethanol-induced secretion of adrenomedullary catecholamines in LS and SS mice is due to differential central nervous system sensitivities to ethanol.

Adrenal Medulla↗
PubMed1985

Effects of nicotine on beta-endorphin, alpha MSH, and ACTH secretion by isolated perfused mouse brains and pituitary glands, in vitro.

The effects of nicotine on secretion of the pituitary peptides beta-endorphin, alpha MSH, and ACTH were studied using the isolated perfused mouse brain (IPMB) and isolated superfused pituitaries of C3H mice. Nicotine (6.1 microM) stimulated secretion of beta-endorphin immunoreactivity from C3H IPMB approximately twofold. Secretion of alpha MSH immunoreactivity was stimulated approximately two- and sixfold by 6.1 microM and 12.2 microM nicotine, respectively. However, nicotine (6.1 microM) had no direct effect on the secretion of beta-endorphin, alpha MSH, or ACTH immunoreactivities from the isolated superfused pituitaries. The data suggest nicotine acts in the brain to stimulate pituitary secretion of alpha MSH and beta-endorphin. Electrocorticographic (ECoG) activity of the IPMB was monitored. Nicotine induced characteristic ECoG changes including a reduction of input voltage, a biphasic response of rapid desynchronization followed by prolonged synchronization, and seizure at high doses (12.2 microM).

Adrenocorticotropic Hormone↗
PubMed1983

Ethanol-induced hyperglycemia mediated by the central nervous system.

A marked difference in ethanol-induced hyperglycemia was found in two lines of mice (LS/Ibg and SS/Ibg) with differential central nervous system sensitivity to ethanol. The LS/Ibg line had a greater sensitivity to the ethanol-induced hyperglycemia, but this difference was not found after administration of hypnotic doses of pentobarbital or halothane. The two lines did not differ in their response to glucose tolerance tests. Fasting, adrenalectomy, and pretreatment with alpha- and beta-adrenergic antagonists (dibenamine and propranolol) eliminated the ethanol-induced hyperglycemic response. Results from intracerebroventricular injections of ethanol indicated that the ethanol-induced hyperglycemia was mediated by the central nervous system.

Animals↗
PubMed1981

Determination of the primary metabolite of central nervous system norepinephrine, 3-methoxy-4-hydroxy-phenethyleneglycol, in mouse brain and brain perfusate by high-performance liquid chromatography with electrochemical detection.

Assays are described for the determination of picomole levels of 3-methoxy-4-hydroxy-phenethyleneglycol (MHPG) in mouse brain and in the perfusate of an intact mouse brain. High-performance liquid chromatography with electrochemical detection yielded a MHPG detection limit of 0.37 pmol. This technique offers a sensitive and inexpensive alternative to gas chromatography with mass spectrometry.

Animals↗
PubMed1981

Characterization of the isolated perfused mouse brain as a system for neurochemical studies.

The preparation of the isolated perfused mouse brain (IPMB) is described along with its electrophysiological, morphological, biochemical and pharmacological properties. Using high performance liquid chromatography with electrochemical detection, the primary metabolite of mammalian central nervous system norepinephrine, 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), was measured in the perfusate at 15-min intervals. The rate of MHPG production was similar to literature values of the rate of norepinephrine turnover in mouse brain. MHPG production rate in the IPMB was blocked by pretreatment with 6-hydroxydopamine and was increased by pretreatment with reserpine.

Animals↗
PubMed1981

Genetic influences on alcohol consumption and actions of alcohol.

Recent studies, utilizing twin pairs and adoption paradymes, have demonstrated hereditary influences on alcohol drinking behavior and on the risk of alcoholism. It is well recognized that alcoholism is a complex condition involving a number of actions of alcohol and alcohol related behaviors. It is not surprising, therefore, that investigations, in man, have demonstrated individual differences in ethanol metabolism and other actions of alcohol and that these individual differences appear to be genetically influenced as well as influenced by environmental factors. Numerous studies have been conducted over the past decade which demonstrate, in animals, a genetic influence on alcohol metabolism and on the actions of alcohol. In this review, the evidence for a genetic influence on central nervous system sensitivity to the effects of alcohol have been discussed including studies with inbred strains of mice and selectively bred lines of mice and rats. The review summarizes studies which suggest a genetic influence on the acquisition of both acute and chronic tolerance to ethanol and upon the display of withdrawal symptoms following the discontinuance of chronic ethanol exposure. It is clear that heredity has ubiquitous influence on alcohol related processes and that these genetic influences are expressed at the behavioral, pharmacological and neurochemical levels.

Alcohol Oxidoreductases↗
PubMed1980

Interrelationships of alcohol consumption, actions of alcohol, and biochemical traits.

Voluntary alcohol consumption, acute tolerance, and central nervous system (CNS) sensitivity to ethanol are potentially informative measures concerning human alcoholism. Little is understood regarding the associations among these parameters or between these traits and neurochemical processes such as brain protein or brain enzyme activities. A powerful strategy is to assess a large number of characteristics simultaneously on all individuals as a heterogeneous sample. This permits rapid screening of a large number of variables with respect to their interrelationships. Identification can thus be made of those variables that are elements of the caudal nexus, and subsequent experimental research can attack the problem of identifying mechanisms. The present study employed mice from the HS/Ibg stock which is maintained by systematic random mating to assure genetic heterogeneity. The results demonstrate that voluntary ethanol consumption and acquisition of acute tolerance to ethanol were positively associated, whereas these measures were not significantly related to CNS sensitivity to ethanol. In addition, ethanol preference was inversely related to soluble brain protein. The activities of the soluble enzymes from brain, aldehyde reductase and glucose-6-phosphate dehydrogenase, were not significantly associated with ethanol preference, acquisition of acute tolerance, or CNS sensitivity to ethanol. Unexpectedly, more than 30 percent of the variance in voluntary alcohol consumption could have been predicted from the measurements of acquisition of acute tolerance, and vice versa.

Alcohol Drinking↗