Recent Developments in the Neurobiology of Alcoholism and Drug Dependence with Focus on the Contributions of European Laboratories

Abstract

The understanding of the neurobiological mechanisms of alcohol and drug dependence has advanced markedly in recent years and this explosion of knowledge has led to new therapeutic strategies especially in the field of relapse prevention (‘anti-craving’ medication). Well-established treatments, e.g. with benzodiazepines, might be replaced by compounds with less abuse liability which have been developed on the basis of our knowledge of the neurobiological mechanisms of addiction. For example, it is now clear that there are many subtypes of ligand- and voltage-gated ion channels and enzyme-coupled receptors. The sensitivity of these transduction mechanisms to alcohol and drugs is subtype dependent. In the coming years new treatment can be expected for addicted subjects of specific indications like, for example, the neurotoxicity of ethanol abuse and the treatment of memory deficits. Such medication is developed based on studies demonstrating that ethanol inhibits glutamate-activated channels, particularly the NMDA subtypes and certain voltage-dependent calcium channels. In contrast to NMDA receptor subtypes, the function of 5-HT₃- and some GABA-activated channels is enhanced by acute ethanol exposure. With chronic exposure, there are often compensatory changes of the transduction mechanisms. Genetic approaches have proven powerful in understanding the role of these mechanisms in ethanol actions and are likely to figure prominently in future research in this area.

Estrategias en el tratamiento de desintoxicación alcohólica

“…La disposición genética para desarrollar la enfermedad alcohólica estaría relacionada con una baja actividad de las neuronas dopaminérgicas mesolímbicas (21) , donde están involucrados tanto los receptores DA1 como DA2, teniendo los primeros una función "permisiva" (22) . Tanto etanol como otras drogas mejoran la transducción de señales eléctricas en las membranas de neuronas ubicadas en el núcleo accumbens a través de una modificación de la concentración de proteínas G -de carácter inhibidor-así como a través de un aumento de la concentración del factor de transcripción FOS y de otros "immediate early gene products" (23) . Además de influir sobre el eje hipotálamo-hipófisis-corteza suprarrenal (24) , el alcohol interacciona con el sistema de opioides endógenos: por una parte, favorece la liberación de péptidos semejantes a beta-endorfinas y met-ence-falinas en el hipotálamo y en el estriado y , por otra, niveles bajos de endorfinas parecen ser un factor de riesgo del alcoholismo (25) ; las dinorfinas resultan ser un freno fisiológico frente a la actividad de las beta-endorfinas, estimuladas éstas por alcohol (26) .…”