A previous study has shown that the stress responsive
neurohormone arginine vasopressin (AVP) is activated in the amygdala during early withdrawal from
cocaine. The present studies were undertaken to determine whether (1) AVP
mRNA levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal (HPA) activity, would be altered during chronic intermittent escalating
heroin administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10 days) spontaneous withdrawal; (2) foot
shock stress would alter AVP
mRNA levels in the amygdala or hypothalamus in rats withdrawn from
heroin self-administration (7 days, 3 h/day, 0.05 mg/kg/infusion); and (3) the selective V1b receptor antagonist
SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter
heroin seeking during tests of reinstatement induced by foot
shock stress and by
heroin primes (0.25 mg/kg), as well as HPA hormonal responses to foot
shock. We found that AVP
mRNA levels were increased during early spontaneous withdrawal in the amygdala only. This amygdalar AVP
mRNA increase was no longer observed at the later stage of
heroin withdrawal. Foot
shock stress increased AVP
mRNA levels in the amygdala of rats withdrawn from
heroin self-administration, but not in
heroin naïve rats. Behaviorally,
SSR149415 dose-dependently attenuated foot
shock-induced reinstatement and blocked
heroin-induced reinstatement. Finally,
SSR149415 blunted the HPA activation by foot
shock. Together, these data in rats suggest that stress responsive AVP/V1b receptor systems (including the amygdala) may be critical components of the neural circuitry underlying the aversive emotional consequences of
drug withdrawal, as well as the effect of negative emotional states on drug-seeking behavior.