Citalopram and Tianeptine: Pharmacological Interventions in alcohol withdrawal-induced negative mood states and serotonin insufficiency in Albino Wistar male rats

Iffat Ara Amjad,Samina Bano Abdul Rub

doi:10.14499/indonesianjpharm30iss2pp75-83

Iffat Ara Amjad, Samina Bano Abdul Rub

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https://doi.org/10.14499/indonesianjpharm30iss2pp75-83

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Abstract

ABSTRACT The present study aims to investigate the neurochemical and behavioural effects of tianeptine and citalopram to block alcohol withdrawal-induced audiogenic seizures in alcohol withdrawal (AW) rats. Citalopram and tianeptine were administered sub-chronically to block AW-induced audiogenic seizures. Brain regional tryptophan (TRP), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined using high-performance liquid chromatography connected to the fluorimetric detector. Citalopram increased brain TRP concentration in all the regions, however, tianeptine increased brain TRP concentration only in amygdala and hippocampus. Increased brain serotonin concentration was seen by citalopram but not by tianeptine in all the regions. Further, tianeptine was shown to increase 5-HT turnover in all the regions, however, citalopram appeared to increase 5-HT turnover only in the hippocampus. It is concluded that the citalopram and tianeptine behave differently on the intrinsic pathway of serotonin metabolism that appeared to be compensated by the release pattern of serotonin. Further, chronic exposure of serotonergic agents causes restoration and structural reforming of serotonin reuptake mechanism that is desensitized following chronic alcohol exposure. Thus the inclusive approach of the serotonergic system plays an undoubted role in the pharmacological management of AW syndrome.

Highlights

Alcohol withdrawal syndrome characterized by a set of symptoms such as tremor, anxiety, restlessness, insomnia that begins as early as 6h after the initial decline from peak intoxication and the seizures may occur in untreated patients in acute alcohol withdrawal
Behavioral adaptation during alcohol dependence involves the activation of corticotrophin releasing hormone (CRH) system (Sarnyai et al, 2001) in the hypothalamus that projects to the serotonergic system in limbic brain areas such as hippocampus and amygdala (Koob, 2000; Oscar- Berman, 2000)
There was shows significant decreases in tryptophan concentration, 5-HT and 5HIAA concentrations in hypothalamus, amygdala, hippocampus regions in alcohol withdrawal rats. These results are in agreement with the findings reported earlier (Ara and Bano, 2015) with the experimental evidences that the abnormal 5-HT functions in alcoholism is associated with a low number of 5-HT transporters binding sites in the living and postmortem brains of alcoholics (Heinz et al, 2000; Kranzler et al, 2002)

Summary

Introduction

Alcohol withdrawal syndrome characterized by a set of symptoms such as tremor, anxiety, restlessness, insomnia that begins as early as 6h after the initial decline from peak intoxication and the seizures may occur in untreated patients in acute alcohol withdrawal. In alcohol withdrawn rats behavioral signs such as audiogenic seizures, locomotor hyperactivity, agitation, and wet dog shakes and tremors have been reported. Behavioral deficit during alcohol withdrawal syndrome in rats (Majchrowicz, 1975; Uzbay and Kayaalp, 1995) constitutes the involvement of both neuroendocrine and serotonergic system. Behavioral adaptation during alcohol dependence involves the activation of corticotrophin releasing hormone (CRH) system (Sarnyai et al, 2001) in the hypothalamus that projects to the serotonergic system in limbic brain areas such as hippocampus and amygdala (Koob, 2000; Oscar- Berman, 2000).

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