Fawn hooded rats are subsensitive to the food intake suppressant effects of 5-HT agonists

Wang, Philip; Aulakh, Charanjit S.; Hill, James L.; Murphy, Dennis L.

doi:10.1007/bf00212855

Cited by 42 publications

(15 citation statements)

References 28 publications

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“…Puerarin suppressed ethanol intake in P rats and Fawn Hooded rats, (4) but at equivalent doses, it had no effect in golden hamsters (12). Because both the P rats (26) and the Fawn Hooded rats (27) originated from a randomly bred Wistar colony, their 5-HT and DA metabolizing enzymes are likely to resemble those of the Wistar rats used in this study in regard to their sensitivity to puerarin inhibition. Hence, the difference in ethanol drinking response to puerarin between rats and golden hamsters may be attributed to the difference in sensitivity of their 5-HT and͞or DA metabolizing enzyme(s) to puerarin inhibition.…”

Section: Biochemistry: Keung and Valleementioning

confidence: 99%

Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria

Keung

Vallée

1998

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

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Daidzin, a major active principle of an ancient Chinese herbal treatment (Radix puerariae) for alcohol abuse, selectively suppresses ethanol intake in all rodent models tested. It also inhibits mitochondrial aldehyde dehydrogenase (ALDH-2). Studies on ethanol intake suppression and ALDH-2 inhibition by structural analogs of daidzin established a link between these two activities and suggested that daidzin may suppress ethanol intake by inhibiting ALDH-2. ALDH-2 is a principal enzyme involved in serotonin (5-HT) and dopamine (DA) metabolism. Thus, daidzin may act by inhibiting 5-HT and DA metabolism. To evaluate this possibility, we have studied the effect of daidzin and its analogs on 5-HT and DA metabolism in isolated hamster and rat liver mitochondria. Daidzin potently inhibits the formation of 5-hydroxyindole-3-acetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC) from their respective amines in isolated mitochondria. Inhibition is concentrationdependent and is accompanied by a concomitant accumulation of 5-hydroxyindole-3-acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. Daidzin analogs that suppress hamster ethanol intake also inhibit 5-HIAA and DOPAC formation. Comparing their effects on mitochondria-catalyzed 5-HIAA or DOPAC formation and hamster ethanol intake reveals a positive correlation-the stronger the inhibition on 5-HIAA or DOPAC formation, the greater the ethanol intake suppression. Daidzin and its active analogs, at concentrations that significantly inhibit 5-HIAA formation, have little or no effect on mitochondria-catalyzed 5-HT depletion. It appears that the antidipsotropic action of daidzin is not mediated by 5-HT (or DA) but rather by its reactive intermediates 5-hydroxyindole-3-acetaldehyde and, presumably, 3,4-dihydroxyphenylacetaldehyde as well, which accumulates in the presence of daidzin.In a recent study, we demonstrated that daidzin, a constituent of an ancient Chinese herbal treatment (Radix puerariae) for alcohol abuse, selectively suppresses home-cage ethanol intake by Syrian golden hamsters under a two-bottle, free choice (ethanol͞water) condition (1). Since then, the ethanol intake suppressive (antidipsotropic) activity of daidzin and the R. puerariae extract have been confirmed by us (2, 3) and other investigators (4-6) independently in golden hamsters, Wistar rats, Fawn hooded rats, and the genetically bred P rats under various experimental conditions, including two-lever choice (ethanol͞starch solution), two-bottle free choice (ethanol͞ water), limited access, and ethanol-deprived paradigms. These laboratory findings are consistent with those of the herbal treatment used in China and thereby suggest that daidzin or one or more of its derivatives and͞or metabolites might be effective in the treatment of alcohol abuse and͞or alcoholism.The mechanism by which daidzin selectively suppresses ethanol intake in laboratory animals is unknown at this time.In an early study, we showed that daidzin is a selective and potent inhibitor of mitochondrial aldehyde dehydrogen...

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Section: Biochemistry: Keung and Valleementioning

confidence: 99%

Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria

Keung

Vallée

1998

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

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“…Reduced cerebrospinal fluid levels of the serotonin metabolite 5-HIAA are observed in some alcoholics (Linnoila et al, 1983), and are associated with increased ethanol consumption in rhesus monkeys (Higley et al, 1996). Ethanol-preferring rats display alterations in tissue serotonin levels (McBride et al, 1990Aulakh et al, 1994;Zhou et al, 1994), responses to serotoninergic agents (Gudelsky et al, 1985;Aulakh et al, 1988aAulakh et al, , b, 1992Aulakh et al, , 1994Wang et al, 1988), serotonin reuptake (Arora et al, 1983;Hulihan-Giblin et al, 1993;Chen and Lawrence, 2000), and serotonin receptor densities (Hulihan-Giblin et al, 1992Wong et al, 1993;McBride et al, 1994McBride et al, , 1997Chen and Lawrence, 2000). A variety of serotonergic agents can reduce voluntary ethanol consumption in animal models and in humans (for a review, see Lovinger, 1999;Myrick et al, 2001), and serotonin receptor gene KOs also affect ethanol self-administration (Crabbe et al, 1996;Risinger et al, 1996Risinger et al, , 1999Risinger et al, , 2000Rubinstein et al, 1997;El-Ghundi et al, 1998;Phillips et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Sex-Dependent Modulation of Ethanol Consumption in Vesicular Monoamine Transporter 2 (VMAT2) and Dopamine Transporter (DAT) Knockout Mice

Hall

Sora²,

Uhl

2002

Neuropsychopharmacol

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Several lines of evidence suggest that monoaminergic systems, especially dopaminergic and serotoninergic systems, modulate ethanol consumption. Humans display significant differences in expression of the vesicular and plasma membrane monoamine transporters important for monoaminergic functions, including the vesicular monoamine transporter (VMAT2, SLC18A2) and dopamine transporter (DAT, SLC6A3). In addition, many ethanol effects differ by sex in both humans and animal models. Therefore, ethanol consumption and preference were compared in male and female wild-type mice, and knockout (KO) mice with deletions of genes for DAT and VMAT2. Voluntary ethanol (2-32% v/v) and water consumption were compared in two-bottle preference tests in wild-type (+/+) vs heterozygous VMAT2 KO mice (+/À) and in wild-type (+/+) vs heterozygous (+/À) or homozygous (À/À) DAT KO mice. Deletions of either the DAT or VMAT2 genes increased ethanol consumption in male KO mice, although these effects were highly dependent on ethanol concentration, while female DAT KO mice had higher ethanol preferences. Thus, lifetime reductions in the expression of either DAT or VMAT2 increase ethanol consumption, dependent on sex.

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“…Blood platelets from FH rats are deficient in storage, release, and uptake of serotonin sites on platelets and in brain tissue of FH rats, although these findings have been disputed [13, 23]. Although brain 5-HT concentrations were not found to be diminished in the brains of FH rats relative to Sprague-Dawley (SD) rats [15], several studies have examined the possibility that FH rats have an altered central nervous system serotoninergic function [II,34], w-Chlorophenylpiperazine (MCPP), a metabolite of the antidepressant trazodone, has been shown to have high affinity for 5-HT receptors in radioligand studies [29]. However, there is a controversy regarding the reported affi nities of piperazine-type 5-HT agonists such as MCPP and w-trifiuoromethylphenylpiperazine (TFMPP) for 5-H Tia and 5-H Tib sites.…”

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confidence: 99%

Differential Neuroendocrine Responses to the 5-HT Agonist m-Chlorophenylpiperazine in Fawn-Hooded Rats Relative to Wistar and Sprague-Dawley Rats

et al. 1988

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The effect of various doses of the 5-HT agonist m-chlorophenylpiperazine (MCPP) on neuroendocrine function (prolactin and corticosterone responses) were compared in three different rat strains: Wistar, Sprague-Dawley (SD), and Fawn-Hooded (FH) rats. Administration of various doses of MCPP produced increases in plasma concentrations of prolactin and corticosterone in all three rat strains. The prolactin responses of FH rats to MCPP were significantly smaller than that of either Wistar or SD rats, while corticosterone responses were equivalent across all three strains. On the other hand, baseline concentrations of corticosterone, but not of prolactin, were significantly higher in FH animals relative to both Wistar and SD animals. There was no significant difference in either baseline hypothalamic concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, or dopamine or brain concentrations of MCPP among these three rat strains. These findings support some other data indicating that FH rats, a strain with a peripheral platelet serotonin storage pool disorder, also possess alterations in some neuroendocrine functions which are modulated by serotonin.

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Fawn hooded rats are subsensitive to the food intake suppressant effects of 5-HT agonists

Cited by 42 publications

References 28 publications

Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria

Daidzin and its antidipsotropic analogs inhibit serotonin and dopamine metabolism in isolated mitochondria

Sex-Dependent Modulation of Ethanol Consumption in Vesicular Monoamine Transporter 2 (VMAT2) and Dopamine Transporter (DAT) Knockout Mice

Differential Neuroendocrine Responses to the 5-HT Agonist m-Chlorophenylpiperazine in Fawn-Hooded Rats Relative to Wistar and Sprague-Dawley Rats

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