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Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants.
Getachew, Bruk; Hauser, Sheketha R; Csoka, Antonei B; Taylor, Robert E; Tizabi, Yousef.
Afiliación
  • Getachew B; Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA.
  • Hauser SR; Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA. Electronic address: shhauser@iupui.edu.
  • Csoka AB; Department of Anatomy, Howard University College of Medicine, Washington, DC, USA.
  • Taylor RE; Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA.
  • Tizabi Y; Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA. Electronic address: ytizabi@howard.edu.
Drug Alcohol Depend ; 175: 133-139, 2017 06 01.
Article en En | MEDLINE | ID: mdl-28414989
INTRODUCTION: Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. METHODS: In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3h daily for 10days (blood alcohol concentration ∼150mg%) followed by daily injection of 10mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. RESULTS: Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. CONCLUSIONS: The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Abstinencia a Sustancias / Receptores Adrenérgicos alfa 2 / Depresión / Imipramina / Antidepresivos Tricíclicos Límite: Animals Idioma: En Revista: Drug Alcohol Depend Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Irlanda
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Abstinencia a Sustancias / Receptores Adrenérgicos alfa 2 / Depresión / Imipramina / Antidepresivos Tricíclicos Límite: Animals Idioma: En Revista: Drug Alcohol Depend Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Irlanda