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

Alén, Francisco; Serrano, Antonia; Gorriti, Miguel Ángel; Pavón, Francisco Javier; Orío, Laura; Heras, Raquel Gómez de; Ramírez-López, María Teresa; Antón, María M.; Pozo, Miguel A.; Fonseca, Fernando Rodrı́guez de

doi:10.1017/s146114571400087x

Cited by 8 publications

(11 citation statements)

References 25 publications

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“…On the one hand, some preclinical studies have demonstrated reductions in alcohol addiction subsequently to the administration of different 5-HT receptors agonists (Naranjo et al, 1986; Higley et al, 1998; Martijena et al, 2005). On the other hand, the possibility that antidepressant treatment might increase susceptibility to alcoholism has been overlooked (Alén et al, 2013, 2014). Moreover, several clinical studies have shown that pathological gambling, associated with elevated compulsivity, frequently co-occurs with major depression (Cunningham-Williams and Cottler, 2001; Baer et al, 2015; Redden et al, 2015; Agarwal et al, 2016; Grant et al, 2016; Rickelt et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

Prados-Pardo

Martín-González

Mora

et al. 2019

Front. Behav. Neurosci.

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Compulsive behavior is observed in several neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), anxiety, depression, phobia, and schizophrenia. Thus, compulsivity has been proposed as a transdiagnostic symptom with a highly variable pharmacological treatment. Recent evidence shows that glutamate pharmacotherapy may be of benefit in impaired inhibitory control. The purpose of the present study was: first, to test the comorbidity between compulsivity and other neuropsychiatric symptoms on different preclinical behavioral models; second, to assess the therapeutic potential of different glutamate modulators in a preclinical model of compulsivity. Long Evans rats were selected as either high (HD) or low (LD) drinkers corresponding with their water intake in schedule-induced polydipsia (SIP). We assessed compulsivity in LD and HD rats by marble burying test (MBT), depression by forced swimming test (FST), anxiety by elevated plus maze (EPM) and fear behavior by fear conditioning (FC) test. After that, we measured the effects of acute administration (i.p.) of glutamatergic drugs: N-Acetylcysteine (NAC; 25, 50, 100 and 200 mg/kg), memantine (3.1 and 6.2 mg/kg) and lamotrigine (15 and 30 mg/kg) on compulsive drinking on SIP. The results obtained showed a relation between high compulsive drinking on SIP and a higher number of marbles partially buried in MBT, as well as a higher percentage of freezing on the retrieval day of FC test. We did not detect any significant differences between LD and HD rats in FST, nor in EPM. The psychopharmacological study of glutamatergic drugs revealed that memantine and lamotrigine, at all doses tested, decreased compulsive water consumption in HD rats compared to LD rats on SIP. NAC did not produce any significant effect on SIP. These results indicate that the symptom clusters of different forms of compulsivity and phobia might be found in the compulsive phenotype of HD rats selected by SIP. The effects of memantine and lamotrigine in HD rats point towards a dysregulation in the glutamatergic signaling as a possible underlying mechanism in the vulnerability to compulsive behavior on SIP. Further studies on SIP, could help to elucidate the therapeutic role of glutamatergic drugs as a pharmacological strategy on compulsive spectrum disorders.

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Section: Discussionmentioning

confidence: 99%

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

Prados-Pardo

Martín-González

Mora

et al. 2019

Front. Behav. Neurosci.

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“…These therapeutics have drawbacks in that it takes weeks to months for a therapeutic response, and nearly 50% of patients show full remission [1,9]. Moreover, drinking alcohol can potentiate the side effects of antidepressants and worsen the symptoms of depression; for example, reuptake inhibitors can increase alcohol seeking behavior [10,11]. In addition, studies have shown that alcohol can lower the seizure threshold for antidepressants that act as monoamine reuptake inhibitors [12].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, studies have shown that alcohol can lower the seizure threshold for antidepressants that act as monoamine reuptake inhibitors [12]. Therefore, these limitations make it difficult to treat and manage alcohol withdrawal dependent affective disturbances [13,10].…”

Section: Introductionmentioning

confidence: 99%

Ketamine administration during a critical period after forced ethanol abstinence inhibits the development of time-dependent affective disturbances

Vranjkovic

Winkler

Winder

2018

Neuropsychopharmacol

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Forced abstinence from chronic two bottle-choice ethanol drinking produces the development of negative affective states in female C57BL/6J mice. We previously reported that this disrupted behavior is acutely reversed by administration of ketamine 30 min-prior to testing. Here we assessed whether ketamine can be used as an inoculant against the development of abstinence- dependent affective disturbances. In parallel, we examined the impact of ketamine administration on long-term potentiation (LTP) in the bed nucleus of the stria terminalis (BNST), a region implicated in affective disturbances. We administered ketamine (3 mg/kg i.p.) to female C57BL/6J mice with a history of chronic ethanol drinking at either the onset, two, or 6 days- post-abstinence and observed its impact on affective behavior in the elevated plus maze (EPM), the Novelty Suppressed Feeding Test (NSFT), and the Forced Swim Test (FST). In addition, we assessed BNST synaptic plasticity with field potential electrophysiology two to 3 weeks into abstinence. We found that early abstinence was associated with disrupted behavior on the EPM. Ketamine administered at the onset of forced abstinence prevented both the deficit in early EPM behavior, and the delayed deficits in NSFT and FST. However, ketamine administered either two or 6 days post-abstinence failed to prevent the abstinence-induced affective disturbances. To begin to explore potential alterations in neural circuit activity that accompanies these actions of ketamine, we assessed the impact of ketamine administration at the onset of forced abstinence and measured LTP induction in the BNST. We find that early ketamine administration persistently increased the capacity for LTP within the BNST. These findings suggest a critical period at the onset of forced abstinence in which ketamine inoculation can prevent the development of affective disturbances, in part by enhancing plasticity within the BNST.

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“…Interestingly, authors also found the same effect in animals under combination of AD (escitalopram) and anti-relapse (acamprosate) treatments. Related to that, subchronic treatment with different ADs (SSRIs and SNRIs) has been demonstrated to augment alcohol consumption in animal models of alcohol deprivation, which were treated along abstinence and re-exposed to alcohol selfadministration once AD treatment ended [113,114].…”

Section: Preclinical Evidence Of Antidepressant Treatment Improves Almentioning

confidence: 99%

Rethinking the Use of Antidepressants to Treat Alcohol Use Disorders and Depression Comorbidity: The Role of Neurogenesis

Ballesta¹,

Alén²,

Fonseca³

et al. 2019

Antidepressants - Preclinical, Clinical and Translational Aspects

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Patients with alcohol use disorders (AUDs) are frequently treated with antidepressant drugs (ADs), but clinical evidence of their efficacy is contradictory. Considering that ADs are thought to produce their therapeutic effects partially by increasing hippocampal plasticity and neurogenesis (HN), and that both AUDs and depression share a potential for the disruption of these neuroplastic processes, one could reasonably wonder whether the poor efficacy of AD treatment could be explained by the inability of these drugs to exert their proper action in patients suffering from AUD or depression. In order to further clarify this question, this chapter aims to examine available data regarding the effect of ADs on behavioral and HN alterations related to alcohol abstinence, as a key period in which the treatment would be implemented and in which their potential effects on alcohol-related problems remain under controversy.

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

Cited by 8 publications

References 25 publications

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

Increased Fear Memory and Glutamatergic Modulation in Compulsive Drinker Rats Selected by Schedule-Induced Polydipsia

Ketamine administration during a critical period after forced ethanol abstinence inhibits the development of time-dependent affective disturbances

Rethinking the Use of Antidepressants to Treat Alcohol Use Disorders and Depression Comorbidity: The Role of Neurogenesis

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