Neurobiology of addiction: neuroanatomical, neurochemical, molecular and genetic aspects of morphine and cocaine addiction. Part III
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Philippe Leff [1] ; Aline Morales [1] ; Juan Carlos Calva [1] ; Mayra Medécigo [1] ; Rodolfo Acevedo [1] ; Armando Valdez [1] ; Carlos Lima [1] ; Benito Antón [1]
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[1] Instituto Nacional de Psiquiatría
Instituto Nacional de Psiquiatría
México
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- Localización: Salud mental, ISSN 0185-3325, Vol. 23, Nº. 5, 2000, págs. 47-57
- Idioma: español
- Enlaces
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Resumen
- español
Las drogas de abuso ilegal, tales como los alcaloides opiáceos y los psicoestimulantes, inducen cambios profundos en los circuitos neuronales donde las drogas ejercen sus efectos psicoadictivos, produciendo a corto y largo plazo importantes cambios de neuroadaptación neuronal así como cambios plásticos en la sinapsis. Estas neuroadaptaciones surgen como respuestas homestásicas que adquieren las neuronas por la continua estimulación de una droga, determinando el aprendizaje de patrones conductuales específicos. Aunque estos cambios neuroadaptativos representan cambios funcionales en el fenómeno adictivo, como es la dependencia y el síndrome de supresión, no explican los mecanismos biológicos implicados en la naturaleza compulsiva del consumo reiterado de una droga.
La mayoría de las drogas de abuso alteran a largo plazo mecanismos moleculares y procesos celulares involucrados con el aprendizaje asociativo. En este contexto, la estimulación continua de los receptores dopaminérgicos D1 /D3 (D1 R/D3 R), la subsecuente activación del sistema intracelular de señalamiento cAMP/PKA/CREB y la alteración progresiva de la expresión de productos genómicos, producen a largo plazo cambios morfológicos, químicos y moleculares en las neuronas dopaminérgicas, que promueven la generación de nuevos contactos sinápticos y/o remodelación de sinapsis preestablecidas
- English
Drugs of abuse, including opiates and psychostimulants, induce both short and long-lasting effects on behavior and similarly exert profound changes in the neural circuits where these drugs operate producing neuronal adaptations and long term changes in synaptic plasticity. Such neuroadaptation occur as homestatic responses to excessive drug stimulation in assotiation with a specific pattern of learned behaviors induced by repeated drug stimulation. Although such neuroadaptive mechanisms may underlie several aspects of drug dependence and withdrawal, they do not account for the compulsive nature of drug seeking behavior or the tendency to relapse. Most drugs of abuse alter a set of molecular mechanisms involved in normal cellular processes that underlie the physiological aspects of learning and memory where stimulation of dopamine D1 receptors, activation of the cAMP/ PKA/CREB intracellular signaling transduction pathway, alteration of gene expression, and the enhanced synaptic rearrangements currently occur in the acquisition of such behaviors. Therefore, drug addiction, as a chronic relapsing disorder, reflects novel adaptative changes occurring in specific patterns of synaptic connectivity as occurs in normal memory formation. Neural mechanisms that underlie both tolerance and sensitization might coexist and one can unmask the expression of the other after abrupt drug cessation (tolerance) or after prolonged removal of drug administration (sensitization). These effects can even persist for a long time after ending drug administration. Although many of the cellular and molecular adaptations elucidated up to date reflect those neuroadaptations that correlate with altered behavior responses during drug addiction, there are still many unsolved non response questions such as; the precise molecular events implicated in the permanente changes in neurons and neural transmission systems that are responsible for the adaptative behavioral responses during relapse, and drug seeking behavior during chronic drug addiction.
- español
