Serotonin Uptake Blockers and Voluntary Alcohol Consumption

Gill, Kathryn; Amit, Zalman

doi:10.1007/978-1-4899-1678-5_12

Cited by 69 publications

(20 citation statements)

References 73 publications

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“…Selective serotonin reuptake inhibitors suppress nondependent alcohol drinking in rats (Gill and Amit, 1989) and early stage problem drinking in humans (Naranjo and Sellers, 1989), but not drinking by laterstage human alcoholics (Kabel and Petty, 1996). Furthermore, low serotonin functioning in humans has long been associated with impulsivity and a predisposition to alcohol dependence (Linnoila et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats

Gilpin²,

Richardson³

et al. 2008

Behavioural Pharmacology

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A 'binge' is defined by National Institute on Alcohol Abuse and Alcoholism as an excessive pattern of alcohol drinking that produces blood-alcohol levels (BALs) greater than 0.08 g% within a 2-h period and may or may not be associated with dependence. The purpose of this investigation was to explore the effects of several neuropharmacological agents in an animal model in which outbred rats voluntarily and orally self-administer pharmacologically meaningful alcohol doses that produce BALs ≥ 0.08 g% in daily limited access two-bottle choice and operant drinking sessions. Rats were trained to self-administer either 10% (w/v) alcohol solution sweetened with 'supersac' (3% glucose + 0.125% saccharin) or supersac alone versus water in a two-bottle choice or operant situation during 30-min daily sessions. Rats were then injected systemically with multiple doses of duloxetine, naltrexone, and the corticotropin-releasing factor antagonist, MPZP, in Latin-square designs. Alcohol binge drinkers reliably consumed amounts of alcohol sufficient to produce BALs ≥ 0.08 g%. Duloxetine dose-dependently suppressed two-bottle choice alcohol binge drinking and operant alcohol responding as well as operant supersac responding, but did not affect two-bottle choice supersac drinking. Naltrexone-suppressed alcohol binge drinking at very low doses and suppressed supersac drinking at moderate-to-high doses. MPZP did not affect alcohol or supersac consumption. Different profiles for drugs that suppress binge-like alcohol drinking compared with dependenceinduced drinking provide a heuristic foundation for future medications development.

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Section: Discussionmentioning

confidence: 99%

Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats

Gilpin²,

Richardson³

et al. 2008

Behavioural Pharmacology

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“…The inhibition of 5-HT reuptake function has complicated the effects on food intake and fluid consumption [152]. SSRIs do suppress food intake [153,154] and fluid consumption [152] and decrease palatability [155].…”

Section: Serotonin Reuptake Inhibitorsmentioning

confidence: 99%

“…SSRIs do suppress food intake [153,154] and fluid consumption [152] and decrease palatability [155]. Yet, motivational factors exert some control on the expression of these behaviors [156].…”

Section: Serotonin Reuptake Inhibitorsmentioning

confidence: 99%

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Johnson

2008

Biochemical Pharmacology

245

185

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The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

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“…Serotonergic pathways originating from raphe nuclei and projecting to the cortex, hippocampus, and subcortical structures can influence drinking behavior in alcohol-dependent individuals (Baumgarten and Grozdanovic, 1997) either directly by modulating alcohol's reinforcing effects or indirectly by mediating impulse control and affective state (Stoltenberg, 2003). Animal studies have documented an inhibitory role for serotonin (5-HT) in regulating alcohol intake (McBride and Li, 1998), and 5-HT reuptake inhibitors reduce ethanol consumption in rats (Gill and Amit, 1989). However, the effectiveness of 5-HT reuptake inhibitors at reducing drinking in humans is not clear.…”

Section: Introductionmentioning

confidence: 99%

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Johnson

Javors

Roache

et al. 2008

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5′-HTTLPR) among healthy control subjects but not alcoholdependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5′-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p < 0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of B max for paroxetine binding, but not V max for serotonin (5-HT) uptake, was lower than that for SS subjects (p < 0.05). More L-carriers than their SS counterparts had V max for 5-HT uptake below 200 nmol/10 7 platelets-min (p < 0.05) and B max for paroxetine binding below 600 nmol/mg protein (p < 0.06). Current drinking (drinks per day during the past 14 days) correlated positively with K m and V max of platelet 5-HT uptake (p < 0.05) and negatively with B max , but not K d , of paroxetine binding (p < 0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with K m and V max of platelet 5-HT uptake (p < 0.05) and B max , but not K d , of paroxetine binding (p < 0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.

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Serotonin Uptake Blockers and Voluntary Alcohol Consumption

Cited by 69 publications

References 73 publications

Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats

Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

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