Abstract
Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.
Highlights
Drug addiction is characterized by relapse to drug-seeking behavior during periods of abstinence [1]
We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls
Tukey post hoc test comparisons revealed that rats quickly learned to self-administer heroin such that a significantly higher number of the active responses and infusions were observed at the fourth training session (P < 0.001) with stable heroin self-administered behavior acquired after the sixth session
Summary
Drug addiction is characterized by relapse to drug-seeking behavior during periods of abstinence [1]. Using the self-administration model of reinstatement, we found that EA attenuates the reinstatement of heroin-seeking behaviors induced by heroin priming [9]. These findings provided new evidence that EA or acupuncture might have therapeutic effect on drug-seeking behaviors. Acupuncture significantly decreased both dopamine release in the NACc and behavioral hyperactivity induced by a systemic morphine challenge [6]. These findings suggest that acupuncture produces a therapeutic effect on opioid or nicotine addiction, possibly by modulating postsynaptic neuronal activity in the NACc (for review, see [19]). Given that there are anatomical differences between NACc core and shell in both neuronal morphology and connectivity, and these subregions play different roles in drug seeking [20,21,22], we applied Fos immunomapping to investigate different functional activation of the NACc core and shell after cueinduced reinstatement of heroin-seeking and EA stimulation
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