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V G Erwin

Publications and source records attributed to V G Erwin.

15 recordsLinked to original sources
PubMed1992

Chronic ethanol consumption produces genotype-dependent tolerance to ethanol in LS/Ibg and SS/Ibg mice.

It is well known that chronic ethanol administration produces tolerance to the sedative-hypnotic and hypothermic effects as well as low-dose locomotor inhibitory effects of ethanol. We report herein characterization of a convenient method of producing genotype-dependent functional tolerance to ethanol-induced locomotor inhibition. Mice, LS/Ibg (LS) and SS/Ibg (SS), which differ markedly in acute effects of ethanol on locomotor activity, hypothermia, and hypnotic sensitivity, were required to consume solutions of ethanol in water as the sole source of liquid. Mice were provided lab chow ad lib. and the following regimen of ethanol in water, v/v: 10% for 4 days, 15% for 4 days, 20% for 7 days, followed by 15% for periods longer than 2 weeks. Control animals received water only or were pair-fed sucrose (isocaloric with ethanol) solutions plus lab chow; both control and ethanol-consuming (15 g ethanol/kg/24 h) mice maintained similar body weights for up to 4 weeks. Blood ethanol concentrations from 10-200 mg% were obtained during a 12 L:12 D cycle. At 6 h following withdrawal, LS and SS mice showed differential dose-dependent tolerance to locomotor inhibitory effects of ethanol. However, low-dose locomotor activation was unaltered in either line of mice, and results indicate that an apparent sensitization in SS mice is secondary to development of tolerance to locomotor inhibition. Maximum tolerance to locomotor inhibition was observed after 2 weeks of chronic ethanol consumption, with responses returning to control values within 1-2 weeks after withdrawal. Rates of acquisition of tolerance were similar in LS and SS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Selective breeding of rats differing in sensitivity to the effects of acute ethanol administration.

Selective breeding of rats for sensitivity to the anesthetic effects of ethanol is being carried out with rats derived from the genetically heterogeneous N/Nih stock. Thirteen generations of within family selection have been achieved with replicate high (HAS), low (LAS) and control alcohol sensitive (CAS) lines. Significant separation between lines on sleep time and blood ethanol concentration (BEC) at awakening following ethanol administration has been achieved. In general, the results obtained so far replicate the findings with short (SS) and long (LS) sleep mice. One exception is that the high alcohol sensitivity rats (HAS) also appear more sensitive to pentobarbital relative to LAS rats. This finding is opposite to that which occurs with SS and LS mice where the low ethanol sensitive SS mice appear more sensitive to pentobarbital than the LS mice.

Alcoholic Intoxication↗
PubMed1991

Regional characterization of brain neurotensin receptor subtypes in LS and SS mice.

Neurotensin (NT) receptor subtypes were investigated in nine brain regions from long sleep (LS) and short sleep (SS) mice that were selectively bred for differences in sensitivity to ethanol. Differences in NT receptor densities may mediate, in part, genetically selected differences in ethanol sensitivity between the two lines of mice. The use of [3H] NT at concentrations from 0.02 to 20 nM yielded biphasic binding isotherms as revealed by Scatchard analysis. Membranes from LS ventral midbrain yielded dissociation constants (KD values) of 0.34 and 3.85 nM for the high (NTH) and low (NTL) affinity components, respectively. SS membranes displayed similar KD values, however the maximum number of binding sites (Bmax) for both receptor subtypes were significantly greater in SS than in LS membranes (46.7 vs. 71.5 fmol/mg protein for NTH and 170.2 vs. 208.2 fmol/mg protein for NTL). Using levocabastine, and H1 antagonist with selectivity for NTL, characterization of NTH and NTL binding in nine brain regions was performed. In general, membranes from each brain region of SS mice had higher densities than LS for both receptor subtypes. Significant differences for the total density of receptors and NTL were found in entorhinal cortex, nucleus accumbens, hippocampus, and ventral midbrain. The only region to differ in NTH was the ventral midbrain. Competition experiments using various NT fragments to compete for NTH binding showed the C-terminal amino acids to be essential for binding. The order of potency was NT1-13 = NT8-13 greater than Neuromedin N greater than NT1-8 = NT1-11.

Alcohol Drinking↗
PubMed1979

Ethanol consumption and hepatic enzyme activity.

Enzyme activity and ethanol consumption were measured in an F2 generation derived from the C57BL and C3H inbred mouse strains. A significant correlation (0.25) was found between alcohol dehydrogenase activity and ethanol acceptance in the F2 generation. Mass selection from a genetically heterogenous mouse stock, HS/Ibg, has yielded high ethanol acceptance (HEA) and low ethanol acceptance (LEA) lines of mice. The mean ethanol acceptance scores for the fifth generation of these lines are 1.008 and 0.606, respectively. The total liver alcohol dehydrogenase activity was found to be 24% higher in the HEA line than in the LEA line after five generations of selective breeding. No association between cytosolic aldehyde dehydrogenase activity and ethanol acceptance was found in either the F2 generation or the fifth generation of the selectively bred lines.

Alcohol Drinking↗
PubMed1976

Effect of hypnotics on mice genetically selected for sensitivity to ethanol.

It was previously shown that the rate of disappearance of blood ethanol was identical for two lines of mice selectively bred for differences in sleep-time after ethanol administration. The ED50 values for the loss of righting response with ethanol were significantly different at 3.64 g per kg for the SS line and 1.65 g per kg for the LS line. In the present study the mean sleep time is 367 sec for SS mice and 9342 sec for LS mice. The ED50 values remain essentially the same as previously reported. Unchanged LD50 values for ethanol, however, are not different at 4.8 g per kg for the SS and 4.5 g per kg for the LS line of mice. The ED50 value for loss for righting response following administration of methanol, butanol and t-butanol is approximately 2 fold greater for the SS line of mice than for the LS line. The ED50 values for sodium pentobarbital or ether in the 2 lines of mice for loss of righting response are virtually identical. In addition, the sleep-time values obtained after the administration of pentobarbital, chloral hydrate, trichloroethanol and paraldehyde are not significantly different. These data indicate that while the SS and LS lines of mice differ in central nervous system sensitivity to ethanol, methanol, butanol and t-butanol it is implied that they do no differ in central nervous system sensitivity to other hypnotic agents tested. Proof of this latter suggestion awaits determination of metabolic rates, and brain levels of these other depressants.

Animals↗
PubMedDate not supplied

Neurotensin modulates K(+)-stimulated dopamine release from the caudate-putamen but not the nucleus accumbens of mice with differential sensitivity to ethanol.

Slices of caudate-putamen (CP) and nucleus accumbens (NA) prepared from Long-Sleep (LS) and Short-Sleep (SS) mice were used to determine the effects of neurotensin (NT) and ethanol on K(+)-stimulated 3H-dopamine (3H-DA) release and to test the hypothesis that ethanol acts, in part, via NT receptor-mediated processes. Slices prepared from either LS or SS CP or NA did not differ in submaximal (25 mM) K(+)-stimulated 3H-DA release but 60 mM K+ induced significantly greater 3H-DA release from LS CP slices compared with SS CP slices. NT had no effect on unstimulated 3H-DA overflow but enhanced 25 mM K(+)-stimulated 3H-DA release from slices of the CP of both lines of mice. Augmentation of DA release by NT from caudate slices was concentration dependent and tetrodotoxin (TTX) insensitive, implicating a role of presynaptic neurotensin receptors located on nigrostriatal DA neurones. In contrast, NT did not enhance K(+)-stimulated 3H-DA release from NA slices from either line of mice. The absence of an NT effect in NA slices was not due to a rapid desensitization of NT receptors but the data were consistent with the absence of presynaptic NT receptors on dopaminergic terminals in the NA. Between-line differences were observed in the effect of ethanol on NT enhancement of 25 mM K(+)-stimulated 3H-DA release from CP slices. Ethanol (100 mM) applied concomitantly with NT blocked the NT enhancement of 3H-DA release from CP slices of LS but not SS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗