Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats

Recent anatomical evidence suggests that the shell of the nucleus accumbens , the bed nucleus of the stria terminalis, and the central nucleus of the a mygdala, together referred to as the extended amygdala, may play a role in opiate dependence. The bed nucleus of the stria terminalis and the shell of the nucleus accumbens have a moderately high density of opiate receptors, which allows for manipulation of opiate neurotransmission with receptor ant agonists. The goal of this study was to determine the role these regions pl ay in opiate reinforcement, and whether dependence alters the reinforcing e ffects of opiates by examining the effect of local administration of the op iate receptor antagonist methylnaloxonium on heroin self-administration in dependent and nondependent rats. Previous studies revealed that blockade of the reinforcing effects of opiates with systemic administration of opiate receptor antagonists results in an increase in heroin self-administration i n nondependent rats, and a greater increase in dependent rats. In the prese nt study, methylnaloxonium dose-dependently suppressed heroin intake when i njected into the bed nucleus of the stria terminalis and shell of the nucle us accumbens of dependent rats, and had no effect in nondependent rats. The se results demonstrate that opiate receptors in parts of the extended amygd ala may be responsible for the reinforcing effects of opiates in dependent animals and suggest that activity in this system may be recruited during th e development of dependence. (C) 2000 Elsevier Science B.V. All rights rese rved.