Individual vulnerability to stress-induced relapse during abstinence from chronic
heroin exposure is a key feature of
opiate addiction, with limited studies on this topic.
Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in
heroin-seeking behavior triggered by foot
shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced
heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including
pro-opiomelanocortin (
POMC),
orexin, plasma
ACTH and
corticosterone, as well as
dopamine D2 receptor (D2) and plasma
prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous
heroin self-administration (SA) and then tested in extinction, and FS-induced and
heroin priming-induced reinstatements. The rats that self-administered
heroin were divided into high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding,
heroin infusion and total
heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP
mRNA levels in medial/basolateral amygdala and lower D2
mRNA levels in caudate putamen. However,
heroin priming resulted in similar reinstatement in both groups and produced similarly low
POMC and high
orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of
heroin- seeking; and 2)
heroin abstinence-associated alterations of hypothalamic
orexin and
POMC expression may be involved in
drug priming-induced
heroin-seeking.