RESUMO
Converging evidence from both preclinical and clinical studies suggests atrial natriuretic peptide (ANP) as a potential target for treatment of alcohol withdrawal and dependence. Since ANP tightly interacts with hypothalamic-pituitary-adrenocortical (HPA) axis activity, especially the modulation of stress-related anxiety during alcohol withdrawal might mediate these effects. We have now evaluated the anxiolytic activity of intraperitoneal ANP application during alcohol withdrawal in alcohol-habituated mice (C57/Bl6J). Anxiety related behaviour was attenuated during ethanol withdrawal following application of ANP (60 µg/kg) vs. saline. Our results support that anxiolytic effects of ANP mediate ANP-related gene effects with clinical data on withdrawal symptomatology.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Fator Natriurético Atrial/uso terapêutico , Etanol/efeitos adversos , Síndrome de Abstinência a Substâncias/complicações , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Animais , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Estatísticas não ParamétricasRESUMO
The persistance of addiction-associated cognitions and behavior is caused, in least part, by long-lasting drug-associated memories. Relapses, triggered by exposure to drug-associated cues, contribute considerably to the maintenance of addiction and are, even after drug-free periods for years, a major challenge in the treatment of addiction. An important advance in understanding the underlying pathophysiology derives from recent research results showing similarities between the process of drug addiction and physiological neural plasticity in learning and memory. In the focus of attention are basic mechanisms involving dopamine, glutamate, and their cellular and molecular targets leading to drug-induced synaptic alterations in the mesolimbic reward system. There is growing evidence from preclinical and clinical studies that specific treatments such as extinction training and cue-exposure therapy are effective. The challenge of future research is to determine which drug-induced adaptations are relevant to the pathophysiology of addiction and to generate more efficient therapies for extinction of addiction-associated cognitions and behavior.
