Serotonergic and adrenergic receptors in alcohol-preferring and non-preferring rats

Wong, David T.; Lumeng, Lawrence; Threlkeld, Penny G.; Reid, Leroy R.; Li, T. K.

doi:10.1007/bf01245714

Cited by 54 publications

(1 citation statement)

References 28 publications

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“…A decrease in the 5-HT release has also been found to occur after prolonged (6 days) administration of ethanol (10 g/kg/day); the inhibitory effect of ethanol appears to be dependent on the impairment of the stimulus-secretion coupling mechanisms (Wu et al, 1986). Other evidence suggesting that ethanol consumption might be related with a decrease in 5-HT brain transmission comes from the fact that binding of 3H-5-HT to 5-HT, receptors is significantly increased in ethanol-preferring rats (Wong et al, 1988). This increase probably indicates up-regulation or supersensitivity of 5-HT, receptors as a compensatory mechanism to the lower levels of the 5-HT in brain areas of the ethanol-preferring rats.…”

Section: Animal Studiesmentioning

confidence: 99%

5-Hydroxytryptamine and alcoholism

Ferreira

Soares‐da‐Silva

1991

Hum. Psychopharmacol. Clin. Exp.

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Ethanol interferes with several brain functions, namely with specific neurotransmission processes. Depletion of brain 5-hydroxytryptamine (5-HT) impairs the acquisition of tolerance to ethanol or facilitates its loss, while activation of 5-HT brain transmission facilitates tolerance development and decreases ethanol consumption. One hypothesis which has been put towards is that genetically determined low 5-HT brain levels may be related to a predisposition to alcoholism. Acute ethanol intake transiently increases brain 5-HT turnover; therefore, ethanol consumption might be hypothesized as an attempt to correct a deficit of 5-HT brain transmission. The findings that administration of selective 5-HT neuronal uptake blockers (zimelidine, citalopram, fluvoxamine and fluoxetine) decrease ethanol intake has given further support to this hypothesis. However, the time course of this effect is different from the antidepressant action described for these compounds. Also, there is evidence to suggest that lower doses of the 5-HT uptake blockers are needed in order to reduce ethanol intake in alcoholic patients; this, however, requires further investigation. Interestingly, other clinical entities which have been found to be associated with a hypothetical dysfunction in 5-HT brain transmission, such as obsessive compulsive disorder, panic disorder and some forms of depression, have also been associated with alcoholism, and seem to respond as well to 5-HT neuronal uptake blockers.

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Section: Animal Studiesmentioning

confidence: 99%

5-Hydroxytryptamine and alcoholism

Ferreira

Soares‐da‐Silva

1991

Hum. Psychopharmacol. Clin. Exp.

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Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms

Krystal

Webb²,

Cooney³

et al. 1994

Arch Gen Psychiatry

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m-Chlorophenylpiperazine produced ethanollike effects and alcohol craving in recently detoxified alcoholics. Yohimbine increased Sensation Scale scores but was not recognized as ethanollike by patients. Although both drugs produced comparable levels of nervousness, yohimbine did not increase craving for alcohol. These data further implicate serotonergic systems in the discriminative properties of ethanol and may indicate a serotonergic contribution to craving. Noradrenergic systems contributed to the discriminative properties of ethanol but not to those features of ethanol response that were salient to craving in this population.

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Effects of gepirone on ethanol consumption, exploratory behavior, and motor performance in rats

Knapp¹,

Benjamin²,

Pohorecky³

1992

Drug Development Research

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Activation of 5-HT receptors via reuptake inhibition, precursor loading, or inhibition of catabolism have consistently resulted in decreases in ethanol preference in rats. The objective of the present studies was to determine whether activation of the EB-HT,~ receptor with gepirone, a selective agonist, decreases ethanol preference. Preference was first evaluated for ethanol solutions from 3 to 11 Yo, in a free-choice situation with ethanol solution or tapwater available in the home cage. Male Sprague-Dawley rats consumed the most ethanol solution relative to water at a concentration of 6%. When ethanol (6% solution) was available to ethanol-habituated rats in a 1 -hr restricted access situation, subjects consumed 5.9 * 0.4 ml. Pretreatment with gepirone (0.46-4.6 mg/kg IP) resulted in a dose-dependent reduction in ethanol consumption in the restricted-access paradigm. The 5-HT reuptake inhibitor fluoxetine also resulted in dose-related decreases in ethanol consumption in restricted access. A subsequent experiment using a lower dose of fluoxetine also found a suppressive effect on ethanol intake. A single daily dose of gepirone failed to decrease the consumption of 6% ethanol when it was continuously available in the home cage. The short half-life of gepirone might explain its lack of effect in continuous access with only one daily dose. Gepirone decreased open-field activity at higher (2.3 to 4.6-mg/kg) doses, but did not affect rotorod performance at any dose (4.6-9.2 mg/kg) tested, whereas haloperidol (0.025-1 .O mg/kg) significantly decreased time on the rotorod. These results suggest that 5-HT,, receptor activation decreases ethanol intake in limited access and that the motorically disrupting effects of gepirone are not manifest under these conditions. 0 1992 Wiley-Liss, Inc.

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Serotonergic and adrenergic receptors in alcohol-preferring and non-preferring rats

Cited by 54 publications

References 28 publications

5-Hydroxytryptamine and alcoholism

5-Hydroxytryptamine and alcoholism

Specificity of Ethanollike Effects Elicited by Serotonergic and Noradrenergic Mechanisms

Effects of gepirone on ethanol consumption, exploratory behavior, and motor performance in rats

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