Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal.

摘要: Although the firing activity of dopamine (DA) neurons in ventral tegmental area (VTA) and behavioral response to morphine rewarding properties alter as opiate withdrawal, little is known about dynamic changes DA signal pathway from VTA nucleus accumbens (NAc) during prolonged whether are indicative vulnerability relapse drug abuse. Here we report that spontaneously withdrawn (SW) rats incapable responding small dose morphine-induced conditioned place preference (CPP) 24h-SW 30d-SW, but recover at 45d-SW. Interestingly, mesoaccumbens signaling, including VTA, contents its metabolic ratio, membrane level D1 receptor NAc elicited by challenge, display a similar pattern time-dependent withdrawal. Moreover, blockade abolishes this transition. In addition, strong correlation was found between % change CPP score induced challenge. These results indicate switch tolerance sensitization which could offer window for therapeutic intervention via manipulations receptors.