The α<sub>1</sub>‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats

Rasmussen, Dennis D.; Alexander, Laura; Raskind, Murray A.; Froehlich, Janice C.

doi:10.1111/j.1530-0277.2008.00829.x

Cited by 89 publications

(121 citation statements)

References 40 publications

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“…However, prazosin was more potent in ethanol-dependent animals, suggesting an increase in the sensitivity to prazosin in dependent animals due to alterations in the norepinephrine system during chronic exposure to ethanol. Then, Rasmussen and colleagues [314] tested the efficacy of prazosin in suppressing alcohol drinking in rats selectively bred for alcohol preference (P line). Adult male P rats were given open access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 hours daily.…”

Section: Alpha-adrenergic Receptormentioning

confidence: 99%

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Leggio¹,

Cardone²,

Ferrulli³

et al. 2010

curr pharm des

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Treating alcohol use disorders represents a main goal in public health, but the effect of current medications is modest. Thus, in the last few years, research has been focusing on identifying new neuropharmacological targets for alcohol dependence. This review will summarize recent research, which has identified new targets to treat alcohol dependence. A variety of systems have been investigated, such as the endocannabinoid system, modulators of glutamatergic transmission, corticotropin-releasing factor (CRF), neuropeptide Y (NPY), nociceptin, glial cell line-derived neurotrophic factor (GDNF), acetaldehyde (ACD), substance P and Neurokinin 1 (NK1) receptor, nicotinic acetylcholine receptors (nAchRs), alpha-adrenergic receptor, and many others. Compared to preclinical studies, only a few clinical studies have been conducted so far. Thus, there is a critical need to translate successful preclinical results into human clinical trials. However, since some clinical studies have failed to replicate preclinical findings, future research will have not only to identify more efficacious medications, but also delineate the best match between a particular pharmacotherapy with a specific alcoholic subtype.

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Section: Alpha-adrenergic Receptormentioning

confidence: 99%

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Leggio¹,

Cardone²,

Ferrulli³

et al. 2010

curr pharm des

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“…Vehicle was 45 mM lactate buffer (pH 5.2). The IP doses of prazosin in this study were the same as the IP doses of prazosin that we have previously demonstrated to decrease alcohol drinking without producing sedation, motor effects, or malaise in male P rats (Rasmussen et al, 2009Froehlich et al, 2015).…”

Section: Drug Treatmentsmentioning

confidence: 99%

“…We previously demonstrated that prazosin treatment acutely and chronically decreases voluntary alcohol drinking in P rats (Rasmussen et al, 2009;Froehlich et al, 2013), alcohol drinking in a rat model of relapse to alcohol drinking (Froehlich et al, 2015), alcohol seeking and drinking in operant paradigms (Verplaetse et al, 2011), and drinking during acute withdrawal in alcoholdependent outbred rats (Walker et al, 2008). Prazosin treatment also facilitates abstinence in treatment-seeking alcohol-dependent men, as demonstrated in a study in which the subjects were unaware of their treatment condition (prazosin vs placebo) and there were no differences in side effects reported (Simpson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations

Rasmussen

Kincaid

Froehlich

2016

Alcohol and Alcoholism

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Aims: Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Methods: Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Results: Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Conclusion: Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Short summary: Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated alcohol deprivations may prevent the increased anxiety that is a risk factor for relapse to alcohol drinking.

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“…An experiment demonstrated that prazosin reduces alcohol self-administration and is more potent in ethanol-dependent rats than in non-dependent, suggesting that prazosin blocks dependence-induced increases for responding to alcohol by rats [100]. Subsequently, an experiment demonstrated that both acute and chronic prazosin treatment decreases ethanol consumption in alcohol preferring rats [101]. Based on this preclinical evidence, a 6-week pilot DBPCRCT was recently performed [102].…”

Section: Prazosinmentioning

confidence: 95%

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

Edwards

Kenna²,

Swift³

et al. 2011

CPD

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Harmful alcohol use is a risk factor in more than 60 diseases and injuries resulting in approximately 2.5 million deaths per year worldwide. In the United States (US) and Europe, there are only a few medications approved for alcohol dependence (AD) however, these medications have only been moderately effective and there is a crucial need for more effective treatments. This review briefly summarizes research on currently approved medications for AD, as well as promising medications like topiramate, baclofen and ondansetron. Topiramate is likely the most promising new treatment for AD, however, further research is needed to determine the optimal dose and appropriate length of treatment. Baclofen, a GABA(B) agonist, is a promising medication as a treatment for AD, especially for patients with AD and severe liver disease. Ondansetron has shown promising results as a potential medication for AD, but only within a certain subtype of individuals. This review also discusses more recent findings on other potential pharmacotherapies for AD, such as serotonin-specific reuptake inhibitors (SSRIs; i.e. sertraline), aripiprazole and prazosin, as well as on some examples of other potentially interesting new neuropharmacological targets (i.e. cannabinoid receptors, CRF, NPY, ghrelin). Finally, the present review also discusses the attempts to personalize medication for AD treatment by alcohol typology and pharmacogenetics.

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The α₁‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats

Cited by 89 publications

References 40 publications

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

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The α1‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats

Cited by 89 publications

References 40 publications

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Turning the Clock Ahead: Potential Preclinical and Clinical Neuropharmacological Targets for Alcohol Dependence

Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations

Current and Promising Pharmacotherapies, and Novel Research Target Areas in the Treatment of Alcohol Dependence: A Review

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The α₁‐Adrenergic Receptor Antagonist, Prazosin, Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats