Increased alcohol consumption in rats after subchronic antidepressant treatment

Abstract

The use of antidepressants for alcoholism in humans has been a matter of controversy in recent years. Despite the existence of an important co-morbidity for depression and alcoholism, some studies suggest that the use of antidepressants could worsen the prognosis of alcoholism. However, there is a lack of studies in animal models exploring this phenomenon. In the present study, we show how the 15-d treatment with fluoxetine (10 mg/kg) or venlafaxine (50 mg/kg) affected alcohol deprivation effect (ADE) and subsequent alcohol consumption. Initially, fluoxetine reduced ADE and venlafaxine did not affect it. However, in the following days, both antidepressants increased alcohol consumption, an effect that was found to last at least 5 wk. Fluoxetine treatment was shown to cause a locomotor sensitized response to a challenge dose of amphetamine (0.5 mg/kg), indicating the presence of a supersensitive dopaminergic transmission. In summary, antidepressant treatment may increase alcohol consumption in rats after a period of alcohol deprivation and this could be related to alterations in the reward circuitry. This finding confirms in an animal model previous reports in humans that may limit the use of antidepressants for alcoholism.

New insights on the antidepressant discontinuation syndrome

“…By creating the expectation of reward that will drive a positive affective state (pleasure, motivation, drive and motivation), the mesolimbic DA pathway plays a prominent role in depression and antidepressant response (Collu et al ., ; Boyer et al ., ; Liu et al ., ; Lane, ). It is of interest then that SRIs (by releasing 5‐HT) adversely affect the neural processing of rewarding and aversive stimuli (Alén et al ., ), possibly resulting in down‐regulation of the reward system (Lane, ). Clinically, SRIs are less effective in managing the anhedonic symptoms of depression (Nutt et al, ; Lane, ) and in fact provoke cognitive and emotional blunting (Sansone and Sansone, ).…”

Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking

“…We elucidated a timeline by examining behavior 1, 15-18, and 35 days after EtOH removal. Treatments with typical antidepressants (selective serotonin reuptake inhibitors (SSRIs)) are notoriously troublesome owing to low treatment efficacy and long lag time (weeks to months) before benefits manifest (Gartlehner et al, 2012), and such antidepressants can escalate EtOH consumption in rats (Alen et al, 2013). We examined alternative pharmacological treatments in reversing depression-like behavior in mice.…”

The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse

“…This hypothesis has been recently addressed in an experimental approach using an animal model of alcoholism (Alén et al, 2013). In that study, the sub-chronic administration of SSRIs (fluoxetine or the noradrenaline/ serotonin reuptake inhibitor venlafaxine) during a period of alcohol deprivation enhanced the alcohol deprivation effect (ADE), leading to a sustained increase in alcohol consumption that lasted at least 5 wk.…”