Pharmacological Treatments for Alcoholism: Revisiting Lithium and Considering Buspirone

Fawcett, Jan; Kravitz, Howard M.; McGuire, Marcella; Easton, Michael; Ross, Jeffrey S.; Pisani, Vincent D.; Fogg, Louis; Clark, David; Whitney, Michael; Kravitz, Glenda; Javaid, Javaid; Teas, Gregory

doi:10.1111/j.1530-0277.2000.tb02038.x

Cited by 34 publications

(12 citation statements)

References 59 publications

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“…A strategy of treating the conse-quence of stress during abstinence has the potential of reducing relapse (see Sinha, 2001). Nonetheless, buspirone, a drug that reduced stress-induced anxiety-like behavior in this investigation, had only limited success in treating alcoholism (Fawcett et al, 2000). Consequently, any future preclinical pharmacological findings predictive of addressing symptoms induced by stress during abstinence will require clinical confirmation.…”

Section: Discussionmentioning

confidence: 83%

Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist

Breese

Overstreet

Knapp

et al. 2005

Neuropsychopharmacol

116

110

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Repeated withdrawals from chronic ethanol induce a persistent adaptive change. Further, stress substitutes for the initial two withdrawals of a multiple-withdrawal protocol to sensitize rats to withdrawal-induced anxiety-like behavior ('anxiety'). Therefore, it was tested whether the persistent adaptation induced by multiple-withdrawal exposures allows stress to elicit anxiety after a period of abstinence. Social interaction was used to assess the degree of anxiety induced by 45 min of restraint stress 3, 7, or 14 days after rats were exposed to multiple withdrawals from a chronic 4.5% ethanol diet. Restraint stress reduced social interaction (ie anxiety-like behavior) at 3, but not at 7 or 14 days, after the multiple withdrawals. No anxiety response was observed in animals that received multiple withdrawals without stress or in animals that received stress when exposed only to control liquid diet. Drugs (ie a CRF 1 -receptor antagonist, a benzodiazepine receptor antagonist, and a 5-HT 1A -receptor agonist) previously demonstrated to block the cumulative adaptation, when administered during repeated withdrawals, prevented stress-induced anxiety-like behavior during abstinence. Additionally, these drugs applied prior to stress in the rats previously exposed to the repeated withdrawal protocol, likewise, minimized stress-induced anxiety. The anxiety following stress during abstinence from previous chronic ethanol exposure is indicative of an interaction of stress with the persistent adaptive change caused by repeated withdrawals. Stress eliciting anxiety-like behavior during abstinence from previous ethanol exposures in rats is consistent with stress inducing anxiety during recovery (sobriety) in the alcoholic, a circumstance that can facilitate craving and relapse.

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Section: Discussionmentioning

confidence: 83%

Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist

Breese

Overstreet

Knapp

et al. 2005

Neuropsychopharmacol

116

110

View full text Add to dashboard Cite

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“…Although early clinical studies used buspirone during acute detoxification (Dougherty and Gates 1990;Tollefson et al 1992), more recent studies with this drug have used chronic regimens in an attempt to prevent alcoholics from relapsing (Malec et al 1996;Fawcett et al 1999;George et al 1999). The failure of these latter studies could have been predicted from the failure of a recent preclinical study that employed chronic as well as acute buspirone treatment (Hedlund and Wahlstrom 1999).…”

Section: Discussionmentioning

confidence: 99%

“…It has been previously determined that buspirone, a 5-HT 1A receptor partial agonist, will reduce the anxiety-like symptoms associated with withdrawal from ethanol (Dougherty and Gates 1990;Lal et al 1991;File et al 1993), but its success as a treatment in alcoholics has been mixed (Bruno 1989;Kranzler and Meyer 1992;Malcolm et al 1992;Tollefson et al 1992;Malec et al 1996;Fawcett et al 1999;George et al 1999). Recently, a selective 5-HT 2C receptor antagonist, but not 5-HT 1A or 5-HT 3 receptor antagonists, blocked the reduction in social interaction following withdrawal from chronic ethanol exposure (Knapp et al 2000).…”

Section: Introductionmentioning

confidence: 99%

A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats

et al. 2003

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Rationale-Repeated withdrawals from chronic forced ethanol exposure sensitize animals to withdrawal-induced deficits in social interaction behavior. The deficits in social interaction behavior following withdrawal from continuous ethanol exposure can be reduced following acute treatments with 5-HT 2C antagonists or 5-HT 1A agonists.Objectives-The present study investigated whether prior treatment with these serotonergic agents during early withdrawals in rats subjected to repeated withdrawals from ethanol exposure would ameliorate the social interaction deficits observed following the final withdrawal.Methods-Sprague-Dawley rats were exposed to three cycles of 5 days forced ethanol (7%, w/v), with 2 days of control diet after the first and second cycles. Drugs were administered IP 4 h after removal of ethanol on the first and second cycles but not the third in one group and 4.5 h after removal of ethanol on the third cycle in another. The social interaction test was performed 5 h after removal of ethanol on the third cycle. Drugs tested included SB-242084, a 5-HT 2C antagonist; buspirone, a 5-HT 1A partial agonist; WAY-100635, a 5-HT 1A antagonist; ketanserin, a 5-HT 2A antagonist; ritanserin, a mixed 5-HT 2A/2C antagonist; and Ro-601075, a 5-HT 2C agonist.Results-Both SB-242084 and buspirone reduced ethanol withdrawal-induced deficits in social interaction when given either acutely 30 min before the test or at 4 h after withdrawal from the first and second cycles. WAY-100635 and ketanserin were completely ineffective regardless of mode of treatment. In contrast, the 5-HT 2C agonist, Ro-601075, accentuated the withdrawal-induced deficit in social interaction behavior in rats exposed to either 4.5 or 7% ethanol diet. Conclusions-These results support the utility of 5-HT 1A agonists and 5-HT 2C antagonists in reducing anxiety-like behavior induced by ethanol withdrawal and reducing the adaptive changes associated with repeated withdrawals.

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“…54 Lithium was not found to be superior to placebo in reducing alcohol consumption in large controlled trials of alcoholism without comorbid psychopathology. 18,55 Several studies indicate that mood disorders not treated with medication, such as major depression, may increase alcohol relapse [56][57][58] and that treatment of mood symptoms leads to significant decrease in use of alcohol or other substances. This is corroborated by our own study and those of others.…”

Section: Commentmentioning

confidence: 99%

Efficacy of Valproate Maintenance in Patients With Bipolar Disorder and Alcoholism

Salloum¹,

Cornelius²,

Daley³

et al. 2005

Arch Gen Psychiatry

247

143

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Pharmacological Treatments for Alcoholism: Revisiting Lithium and Considering Buspirone

Abstract: These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Cited by 34 publications

References 59 publications

Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist

Prior Multiple Ethanol Withdrawals Enhance Stress-Induced Anxiety-Like Behavior: Inhibition by CRF1- and Benzodiazepine-Receptor Antagonists and a 5-HT1a-Receptor Agonist

A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats

Efficacy of Valproate Maintenance in Patients With Bipolar Disorder and Alcoholism

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