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Stimolazione da etanolo del sistema dopaminergico mesolimbico: ruolo dell'acetaldeide

Sirca, Donatella (2007) Stimolazione da etanolo del sistema dopaminergico mesolimbico: ruolo dell'acetaldeide. [Doctoral Thesis]

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Abstract

Evidence shows that acetaldehyde (ACD), the main metabolite of alcohol previously considered only a toxic substance, may actually mediates the reinforcing effects of ethanol (EtOH) (1). Accordingly, in rodents ACD is self-administred and stimulates the firing of Ventral Tegmental Area (VTA) mesolimbic dopaminergic neurones (2,3). Moreover, recent data show that ACD blockade by sequestration with D-penicillamine or by alcohol dehydrogenase competitive inhibition with 4-methylpyrazolean prevent various electrophysiological and behavioral effects of EtOH (3,4). In this study, we used in vivo microdialysis to measure dopamine (DA) output in the Nucleus Accumbens shell (Nacbs) of male albino Wistar rats in response to a challenge with ACD and EtOH. Both EtOH (0.5, 1.0, 2.0 g/kg) and ACD (10,20 40 mg/kg) were administered by gavage (i.g.) in order to mimic the route of administration used by humans. To further research the effect of ACD on the mesolimbic DAergic system, ACD (50, 75, 100 µM) was administered via reverse dialysis within the VTA while measuring DA output in the NAcbs. Intragastric EtOH and ACD administration dose-dependently increased DA extracellular levels in (i.g. administration) was more potent than EtOH, eliciting similar effects on DA outflow in the NAcbs at doses 50-fold lower. These findings support the hypothesis that ACD has central nervous system effects in its own right and show that ACD stimulates mesolimbic DAergic neurons by an NAcbs. Our results, togheter with the data in the literature, allows to conclude that ACD plays a key role in the EtOH-induced stimulation of mesolimbic pathway and possibly in its rewarding and motivational properties. 1) Quartemont et Al., TIPS 25(3): 130-4, 2004 2) Rodd-Henricks et Al., PBB 72:55-64, 2002 3) Foddai et Al., Neuropsych. 29(3): 530-6, 2004 4) Font et Al., Neuropsych. 184(1): 56-64, 2005

Item Type:Doctoral Thesis
Date:18 December 2007
Tutor:Diana, Marco, Enrico, Paolo
PhD classes:Ciclo 20 > Farmacologia delle tossicodipendenze
Coordinator:Di Chiara, Gaetano
Institution:Universita' degli Studi di Cagliari
Divisions:Dipartimenti (fino a dicembre 2011) > Dipartimento di Tossicologia
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Uncontrolled Keywords:Ethanol, Acetaldehyde, Dopamine
ID Code:75
Deposited On:29 Oct 2008 10:52

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