Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization.
Neuropsychopharmacol. 2006-04-26; 32(3): 616-624
DOI: 10.1038/sj.npp.1301083
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Increased drug availability can precipitate a rapid transition to compulsive drug
use in both vulnerable humans and laboratory animals. Recent studies have shown
that despite equivalent levels of psychomotor sensitization, only rats with
prolonged, but not limited, access to cocaine self-administration respond to the
priming effects of cocaine on drug seeking, as measured in a within-session
reinstatement model of drug craving. In this model, drug seeking is first
extinguished and then reinstated by non-contingent presentations of the drug
alone in the absence of response-contingent stimuli. Here, we assessed the
generality of this observation in rats with daily short (1 h, ShA) vs long access
(6 h, LgA) to i.v. heroin self-administration. As expected, heroin intake by LgA
rats (n=24) increased over time to become excessive compared to heroin intake by
ShA rats (n=24). After escalation, LgA rats tended to be less sensitive to
heroin-induced locomotion (7.5-30 microg, i.v.) than ShA rats. In contrast, only
LgA rats, not ShA rats, responded to the priming effects of heroin, as measured
by the ability of heroin alone (7.5-30 microg, i.v.) to reinstate extinguished
drug-seeking behavior. Finally, during the course of heroin intake escalation, a
large proportion of LgA rats developed self-injury (mostly targeting the nails
and digit tips of the forepaws), a negative consequence not seen in ShA rats.
This study reproduces and extends previous research on compulsive cocaine use by
showing that heroin-induced reinstatement is also specific to compulsive drug use
and dissociable from heroin-induced reward and psychomotor sensitization.