"El circuito motivador y sus interconexiones en el fenómeno de sensibilización producido por la 3,4-metilendioximetanfetamina (mdma, ""éxtasis"") en rata"

Resumo

EL CIRCUITO MOTIVADOR Y SUS INTERCONEXIONES EN EL FENÓMENO DE SENSIBILIZACIÓN PRODUCIDO POR LA 3,4-METILENDIOXIMETANFETAMINA (MDMA, "ÉXTASIS") EN RATA. RESUMEN: Studies on the role of the motive Circuit and its connections in 3,4-methylendioxymethamphetamine (MDMA)-induced behavioral sensitization in rats 3,4-Methylenedioxymethamphetamine is an amphetamine derivative with high abuse liability despite its potential neurotoxic effects and psychiatric complications reported in recreational MDMA users. Akin to amphetamine and cocaine, MDMA elicits long-term behavioural and neurochemical sensitization in rats. This phenomenon has been considered a useful animal model for the development of psychosis. However, recent studies have al so emphasised that neuronal plasticity underlying sensitization results in the enhancement of the incentive motivational effects of psychostimulants, which contributes to drug craving. This work was aimed at studying the mechanisms underlying MDMA-induced behavioural sensitization. We first focused our investigation at the mesoaccumbens dopaminergic system, because of its crucial role in the behavioural sensitization induced by other drugs of abuse. Our results indicate that the systemic administration of the dopamine Di receptor antagonist SCH23390 blocks the expression but not the development of MDMA sensitization. This is in agreement with what has been reported for cocaine. Similarly, when SCH23390 was locally applied into the core of NAc the expression of MDMA sensitization was inhibited as well. These data suggest that blockade of Di receptors located in this brain region are responsible for the results obtained after the systemic administration of SCH23390. In a second set of experiments we also tested whether Di receptors located in the medial prefrontal cortex (mPFC) could contribute to the results achieved after systemic SCH23390. Administration of SCH23390 into the mPFC blocked the expression of MDMA sensitization; however, such effect was mediated by 5-HT2C receptor stimulation excluding any role for mPFC Di receptor blockade. Finally, excitotoxic lesions of the mdPFC were carried out in order to analyse its contribution in the general mechanisms of MDMA sensitization. Both the development and expression of MDMA-induced behavioural sensitization were prevented supporting the key role of this brain region in MDMA sensitization.