The effect of halothane on mice selectively bred for differential sensitivity to alcohol

Baker, Rodney C.; Melchior, Christine L.; Deitrich, Richard A.

doi:10.1016/0091-3057(80)90150-1

Cited by 46 publications

(4 citation statements)

References 22 publications

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“…sleep time) to ethanol [35]. However, the LS and SS mice do not differ in CNS sensitivities to pentobarbital or halothane [2,15,41], nor do these drugs elicit a differential hypothermic or hy perglycemic response in these lines of mice [2,63]. In the present study, neither halothane nor pentobarbital elicited a differential elevation in plasma corticosterone in LS and SS mice.…”

Section: Discussioncontrasting

confidence: 34%

“…Subsequent investigations have shown that these lines of mice differ in central nervous system (CNS) sensitivities to the depressant actions of ethanol, inasmuch as the two mouse lines exhibit little difference in several important pa rameters including rate of ethanol metabolism [20] and sleep time values obtained with chemically diverse CNS de pressants [2,15]. LS mice exhibit a greater sensitivity than SS mice not only to the depressant effects of ethanol, but also to ethanol-induced adrenomedullary secretion [63] and adrenocortical activation [25,64], In the latter studies [64], the authors demonstrated that differential ethanol-induced elevation in plasma corticosterone is primarily due to a…”

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confidence: 99%

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Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

Jm¹,

Vg²

1987

Neuroendocrinology

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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 α₂-adrenergic agonist, blocked ethanol-induced elevations in plasma corticosterone in a dose-dependent manner (1 and 10 µg) in LS mice; however, only the 10-µg 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 α₂-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 α-adrenergic antagonist, and propranolol, a β-adrenergic antagonist at high doses (10 µg), produced slight increases in plasma corticosterone in LS mice only. Neither these compounds nor methoxamine, a nonspecific α-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. These results suggest that adrenocortical activation produced by ethanol may be mediated primarily through central noradrenergic systems and that differences in these systems may account for the differential ethanol-induced elevation in plasma corticosterone exhibited by LS and SS mice.

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Section: Discussioncontrasting

confidence: 34%

mentioning

confidence: 99%

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

Jm¹,

Vg²

1987

Neuroendocrinology

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“…Firstly, we imaged alcohol naïve subject, which permits ruling out any direct interfering action of alcohol metabolism with the anaesthetic used. Secondly, animal studies show that halothane does not necessarily exert significant interactions with the central mediators of alcohol effects (Baker et al, 1980; Baker and Deitrich, 21995). Moreover, inter-strain differences in sensitivity to anaesthesia would be expected to produce generalized cortical alterations (Alkire et al, 1999; Heinke and Schwarzbauer, 2002) as well as differences in functional cardiovascular parameters such as blood pressure (Gelman et al, 1984; Steffey et al, 2003), two findings in contrast with the exquisitely focal bCBV effect observed in msP rats, and the observation of comparable blood pressure between the two groups of animals.…”

Section: 4 Discussionmentioning

confidence: 99%

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction

et al. 2013

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Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in e Marchigian Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced gray matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn gray matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction.

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“…Rodent strains that were selectively bred for sensitivity to N 2 O or to nonanesthetic nervous system depressants express only small, and for the most part statistically insignificant, differences in their sensitivity to VAs (11)(12)(13)(14)(15). No loci controlling these small differences in anesthetic sensitivity have been mapped.…”

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confidence: 99%

Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans

Swinderen

Shook²,

Ebert³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Genetic analysis is an essential tool for defining the molecular mechanisms whereby volatile anesthetics (VA) disrupt nervous system function. However, the degree of natural variation of the genetic determinants of VA sensitivity has not been determined nor have mutagenesis approaches been very successful at isolating significantly resistant mutant strains. Thus, a quantitative genetic approach was taken toward these goals. Recombinant-inbred strains derived from two evolutionarily distinct lineages of the nematode Caenorhabditis elegans were tested for sensitivity to clinically relevant concentrations (0.3-0.5 mM) of the VA halothane. The halothane sensitivities of coordinated movement and male mating behavior were highly variant among the recombinant-inbred strains with a range of EC 50 values of 13-and 4-fold, respectively. Both traits were highly heritable (H 2 ‫؍‬ 0.82, 0.87, respectively). Several strains were found to be significantly resistant to halothane when compared with the wild-type strain N2. A major locus or loci mapping to the middle of chromosome V accounted for more than 40% of the phenotypic variance for both traits. Five weaker loci, four of which interact, explained most of the remaining variance. None of the halothane-sensitivity quantitative trait loci significantly affected behavior in the absence of halothane or halothane's potency for C. elegans immobilization, which requires 5-fold higher drug concentrations. Thus, the quantitative trait loci are unlikely to result from differences in halothaneindependent (native) behavior or differences in halothane metabolism or permeability. Rather, these loci may code for targets and͞or downstream effectors of halothane in the C. elegans nervous system or for modifiers of such gene products.

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The effect of halothane on mice selectively bred for differential sensitivity to alcohol

Cited by 46 publications

References 22 publications

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

Central Mechanisms of Ethanol-Induced Adrenocortical Response in Selectively Bred Lines of Mice

Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction

Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans

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