Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

O'Brien, Emmanuelle Simon; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux‐Cantin, Stéphanie; Pierrefiche, Olivier; André, Étienne; Naassila, Mickaël

doi:10.1038/npp.2011.37

Cited by 51 publications

(37 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the two animal experiments, there was no systematic pattern to changes in food intake and body weight that would support the general supposition that high doses of the drugs either singly or in combination may reduce general consummatory behavior. Lastly, since neither desipramine, nor paliperidone, have been reported to alter the metabolism or clearance of alcohol (Monostory et al , 2004, Simon O'Brien et al , 2011) the decrease in alcohol drinking is probably not due to altered alcohol pharmacokinetics.…”

Section: Discussionmentioning

confidence: 99%

Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Chau

Khokhar

Gulick

et al. 2015

Journal of Psychiatric Research

View full text Add to dashboard Cite

Alcohol use disorder commonly occurs in patients with schizophrenia and dramatically worsens their course. The atypical antipsychotic clozapine has been associated with reduced drinking in these patients, but its toxicity reduces its use. We have attempted to create a clozapine-like drug by combining agents that capture components of clozapine’s pharmacologic action, including its weak dopamine D2 blockade and noradrenergic modulation. The current study assessed whether paliperidone, a dopamine D2 receptor and adrenergic alpha-2 receptor antagonist like clozapine, would attenuate alcohol drinking in the alcohol-preferring P rat and the Syrian golden hamster, and whether desipramine, a norepinephrine reuptake inhibitor, would potentiate the ability of paliperidone to attenuate alcohol drinking in the P rat and the Syrian golden hamster. Daily subcutaneous injections of paliperidone (5 mg/kg for the rat; 1 mg/kg for the hamster) over 20 days slightly and transiently attenuated initiation of alcohol consumption in both animals. Desipramine (3 mg/kg) or lower doses of paliperidone alone did not affect alcohol drinking. However, the combination of desipramine (3 mg/kg) and paliperidone essentially prevented initiation of alcohol drinking and acquisition of alcohol preference in the P rat (2.5 or 5 mg/kg), and almost as dramatically suppressed chronic alcohol intake and alcohol preference in the hamster (2.5 mg/kg). Taken together, the current data suggest that (1) the desipramine and paliperidone combination attenuates alcohol drinking in a synergistic manner, and (2) desipramine and paliperidone may serve as an effective new treatment for alcohol use disorder in patients with schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Chau

Khokhar

Gulick

et al. 2015

Journal of Psychiatric Research

View full text Add to dashboard Cite

show abstract

“…Similarly, β1/2-AR antagonists have been used clinically to treat anxiety associated with alcohol withdrawal (Bailly et al, 1992; Sellers et al, 1977), and decrease operant responding for ethanol in a rodent model of dependence (Gilpin and Koob, 2010). SNRIs have shown promise in reducing anxiety-related alcohol intake, reportedly lessening alcohol craving and anxiety following withdrawal in clinical populations (Kim et al, 2005; Liappas et al, 2005; Petrakis et al, 2012) and likewise attenuating anxiety-like behavior, ethanol drinking and the symptoms of acute withdrawal in rodents (Ji et al, 2008; Mochizuki et al, 2002; Saglam et al, 2004; Simon O’Brien et al, 2011). Furthermore, we recently reported that prazosin and duloxetine, when delivered chronically, decrease home-cage ethanol intake and anxiety-like behavior in rats displaying relatively high levels of antecedent anxiety (Skelly and Weiner, 2014).…”

Section: Discussionmentioning

confidence: 99%

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

et al. 2015

View full text Add to dashboard Cite

Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress.

show abstract

“…Previous literature has indicated that DMI can reduce alcohol drinking (McBride et al, 1988; Mason et al, 1996; Goldstein et al, 2004; Simon O'Brien et al, 2011), but at doses that may confer increased risk of cardiovascular toxicity (Pacher and Kecskemeti, 2004). The dose range for DMI treatment in humans is generally 150–200 mg/day (which converts to approximately 15–18 mg/kg in the hamster (Reagan-Shaw et al, 2008)).…”

Section: Discussionmentioning

confidence: 99%

Desipramine enhances the ability of risperidone to decrease alcohol intake in the Syrian golden hamster

Gulick

Chau

Khokhar

et al. 2014

Psychiatry Research

View full text Add to dashboard Cite

The atypical antipsychotic clozapine reduces alcohol drinking in patients with schizophrenia. We have proposed that clozapine’s ability to decrease alcohol drinking relates to its weak blockade of the dopamine D2 receptor and potent blockade of the norepinephrine α-2 receptor, as well as its ability to elevate plasma and brain norepinephrine. Another atypical antipsychotic, risperidone, which is a potent blocker of both the dopamine D2 receptor and norepinephrine α-2 receptor, does not decrease alcohol drinking. In this study, we used the Syrian golden hamster to test whether the ability of risperidone to reduce alcohol drinking would be enhanced if it were used in combination with the norepinephrine reuptake inhibitor desipramine. Hamsters were given free access to water and alcohol (15% v/v) until they reached a steady drinking baseline. They were then treated daily with each drug or drug combination for 20 days. Risperidone (0.2 mg/kg) only transiently decreased alcohol drinking. However, 5.0 mg/kg, and possibly 1.0 mg/kg, desipramine added to 0.2 mg/kg risperidone appeared to produce a more substantial and relatively sustained effect than risperidone alone. Data from this study provides leads toward the development of new treatments for patients with schizophrenia and alcoholism, and also for those with alcoholism alone.

show abstract

Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

Cited by 51 publications

References 71 publications

Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Desipramine enhances the ability of paliperidone to decrease alcohol drinking

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

Desipramine enhances the ability of risperidone to decrease alcohol intake in the Syrian golden hamster

Contact Info

Product

Resources

About