Effects of the Alpha-1 Antagonist Prazosin on KOR Agonist-Induced Reinstatement of Alcohol Seeking.

摘要: BACKGROUND Stress is associated with relapse to alcohol seeking during abstinence, but the processes underlying this relationship are poorly understood. Noradrenaline a key transmitter in stress responses and stress-induced drug seeking. The alpha-1 adrenoceptor antagonist prazosin has been investigated as treatment for alcoholism chronic disorders that frequently comorbid alcoholism. In rats, we previously showed blocks reinstatement of induced by footshock yohimbine stressors reduces yohimbine-induced brain activation. role adrenoceptors other not known. Our most recent work on kappa opioid receptors have reported selective receptor agonist U50,488 induces neuronal activation stress- relapse-related regions. Here determine involvement U50,488. METHODS We trained male Long-Evans rats self-administer (12% w/v), extinguished alcohol-reinforced responding, then determined effects (1 mg/kg) (2.5 mg/kg)-induced regional Fos expression. RESULTS Prazosin blocked U50,488-induced decreased expression orbitofrontal cortex, nucleus accumbens core, ventral bed stria terminalis, central basolateral amygdalar nuclei tegmental area. CONCLUSIONS These findings suggest may reduce inhibiting activity 1 or more these areas.