The Journal of Neuroscience, 2001, 21:RC129:1-5
RAPID COMMUNICATION
Leptin Attenuates Acute Food Deprivation-Induced Relapse to
Heroin Seeking
Uri
Shalev,
Jasmine
Yap, and
Yavin
Shaham
Behavioral Neuroscience Branch, National Institute on Drug
Abuse/Intramural Research Program, Baltimore, Maryland 21224
Studies in rats have shown that intermittent footshock stress
reinstates drug seeking after prolonged drug-free periods. Recently, we
found that another environmental stressor, acute 1 d food
deprivation, potently reinstates heroin seeking in rats. Here we report
that this effect of food deprivation can be blocked by leptin, a
hormone involved in the regulation of energy balance and food intake. Rats were trained to self-administer heroin (0.05-0.1 mg/kg, i.v., per
infusion, three 3 hr sessions per day) for 8-10 d. The
heroin-reinforced behavior was then extinguished for 10-13 d, during
which lever presses had no reinforced consequences. Subsequently, rats
were tested for reinstatement after 1 d of food deprivation
(experiment 1) or exposure to intermittent footshock (15 min,
0.6 mA) and heroin priming injections (0.25 mg/kg, s.c.) (experiment
2). Acute food deprivation reinstated heroin seeking, an effect that
was attenuated by leptin (2 or 4 µg/rat, i.c.v.; two infusions, given 21 hr and 20-30 min before the start of the test sessions). In contrast, leptin had no effect on reinstatement of heroin seeking induced by intermittent footshock or priming injections of heroin. These data indicate that food deprivation can provoke relapse to heroin
seeking via a leptin-dependent mechanism, which is not involved in
relapse induced by footshock stress or reexposure to heroin.
Key words:
extinction; food deprivation; heroin self-administration; leptin; reinstatement; relapse; stress
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