Effect of p-chlorophenylalanine on the acquisition of tolerance to ethanol and pentobarbital

Frankel, David; Jm, Khanna; Ae, LeBlanc; Kalant, H.

doi:10.1007/bf00428901

Cited by 63 publications

(8 citation statements)

References 14 publications

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“…A long history of research using animal models has reported a role for the serotonin system in regulating virtually every aspect of the progression to alcohol dependence, including intake, preference, tolerance, and withdrawal (Myers and Veale, 1968; Griffiths et al, 1974; Frankel et al, 1975; Richardson and Novakovski, 1978). Despite an abundance of studies, the relationship between ethanol and serotonin remains unclear (for review LeMarquand et al, 1994; Kenna, 2010; Sari et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Chronic Ethanol Self-Administration on Hippocampal Serotonin Transporter Density in Monkeys

Burnett¹,

Davenport²,

Grant³

et al. 2012

Front. Psychiatry

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Evidence for an interaction between alcohol consumption and the serotonin system has been observed repeatedly in both humans and animal models yet the specific relationship between the two remains unclear. Research has focused primarily on the serotonin transporter (SERT) due in part to its role in regulating extracellular levels of serotonin. The hippocampal formation is heavily innervated by ascending serotonin fibers and is a major component of the neurocircuitry involved in mediating the reinforcing effects of alcohol. The current study investigated the effects of chronic ethanol self-administration on hippocampal SERT in a layer and field specific manner using a monkey model of human alcohol consumption. [3H]Citalopram was used to measure hippocampal SERT density in male cynomolgus macaques that voluntarily self-administered ethanol for 18 months. Hippocampal [3H]citalopram binding was less dense in ethanol drinkers than in controls, with the greatest effect observed in the molecular layer of the dentate gyrus. SERT density was not correlated with measures of ethanol consumption or blood ethanol concentrations, suggesting the possibility that a threshold level of consumption had been met. The lower hippocampal SERT density observed suggests that chronic ethanol consumption is associated with altered serotonergic modulation of hippocampal neurotransmission.

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Section: Introductionmentioning

confidence: 99%

The Effects of Chronic Ethanol Self-Administration on Hippocampal Serotonin Transporter Density in Monkeys

Burnett¹,

Davenport²,

Grant³

et al. 2012

Front. Psychiatry

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“…1979]. Similarly, ad ministration of L-tryptophan [Z.i>etal., 1979] or task performance under the influence of ethanol [LeBlancet al" 1976] accelerated the acquisition of ethanol tolerance in rats, while treatment with p-chlorophenylalanine slow ed the development of tolerance [Frankel et al, 1975].…”

Section: Discussionmentioning

confidence: 99%

“…The state of isolation represents a whole spectrum of physiological changes. Among them is a decrease in adrenal size and plasma corticosterone level [Louch and Higginbo tham, 1967], Changes in brain neurotrans mitter metabolism have also been investi gated, including changes in the turnover rate of brain serotonin [Garattini et al" 1967;ValzelU and Bernasconi, 1979] and catechol amines [Garattini et al, 1969;Welch and Welch, 1971], Several studies have shown that brain serotonergic and noradrenergic mechanisms are involved in the develop ment of ethanol tolerance [Frankel et al, 1975[Frankel et al, , 1978Ritzmann and Tabakoff, 1976;Sze, 1977], Therefore, further studies which will tie the isolation-induced neurochemical events and the tolerance changes in causal relationship seem pertinent. Such studies will contribute to our understanding of the mech anisms mediating the development of alco hol tolerance.…”

Section: Discussionmentioning

confidence: 99%

Accelerated Acquisition of Ethanol Tolerance in Isolated Mice

Yanai

Sze²

1982

Neuropsychobiology

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Male mice were kept in isolation (isolated mice) or in groups of 8 mice per cage (grouped mice). After 6 weeks all mice received two daily intraperitoneal injections of 3.5 g/kg ethanol at 8 a.m. and 5 p.m., and sleep time was monitored after the a.m. injection. Brain ethanol levels upon awakening were assayed in sample groups. This procedure was repeated for 3 consecutive days. Isolated mice had a shorter sleep time than grouped mice (p < 0.001) and they woke up with higher brain ethanol levels (p < 0.01). Both groups had a progressive decline in sleep time during repeated ethanol exposure (p < 0.001). However, isolated mice achieved the reduction in half the time it took grouped mice (p < 0.001). The sleep time significantly correlated with brain ethanol levels upon awakening (r = –0.4967, p < 0.001). It is suggested, therefore, that isolation in mice reduces brain sensitivity to ethanol and accelerates the rate of acquisition of functional tolerance to ethanol.

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“…The first evidence that chronic consumption of ethanol and the development of tolerance to the effects of ethanol in animals might have to do with 5-HT neurotransmission was provided by Frankel et al (1975). These authors have shown that inhibition of 5-HT synthesis by p-chlorophenylalanine impaired the acquisition of tolerance to the effects of ethanol.…”

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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Effect of p-chlorophenylalanine on the acquisition of tolerance to ethanol and pentobarbital

Cited by 63 publications

References 14 publications

The Effects of Chronic Ethanol Self-Administration on Hippocampal Serotonin Transporter Density in Monkeys

The Effects of Chronic Ethanol Self-Administration on Hippocampal Serotonin Transporter Density in Monkeys

Accelerated Acquisition of Ethanol Tolerance in Isolated Mice

5-Hydroxytryptamine and alcoholism

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