Acupuncture Stimulation Attenuates Impaired Emotional-Like Behaviors and Activation of the Noradrenergic System during Protracted Abstinence following Chronic Morphine Exposure in Rats
The purpose of this study was to evaluate whether acupuncture stimulation attenuates withdrawal-induced behaviors in the rats during protracted abstinence following chronic morphine exposure. To do this, male rats were first exposed to morphine gradually from 20 to 100？mg/kg for 5 days, and subsequently naloxone was injected once to extend despair-related withdrawal behaviors for 4 weeks. Acupuncture stimulation was performed once at the SP6 (Sanyinjiao) acupoint on rat’s; hind leg for 5？min during protracted abstinence from morphine. The acupuncture stimulation significantly decreased despair-like behavior deficits in the forced swimming test and low sociability in the open-field test as well as increased open-arm exploration in the elevated plus maze test in the last week of 4-week withdrawal period. Also the acupuncture stimulation significantly suppressed the increase in the hypothalamic corticotropin-releasing factor (CRF) expression, the decrease in the tyrosine hydroxylase expression in the locus coeruleus, and the decrease in the hippocampal brain-derived neurotrophic factor mRNA expression, induced by repeated injection of morphine. Taken together, these findings demonstrate that the acupuncture stimulation of SP6 significantly reduces withdrawal-induced behaviors, induced by repeated administration of morphine in rats, possibly through the modulation of hypothalamic CRF and the central noradrenergic system. 1. Introduction Morphine, a strong pain reliever, is widely used to treat moderate to severe pain as well as a number of other pathological indications. The continuous use of morphine causes drug craving, tolerance to opiate analgesia, and a withdrawal syndrome, particularly a relapse into drug-seeking behavior, when the drug is discontinued [1]. Accordingly, the abuse of morphine and subsequent withdrawal from it result in an aversive emotional state and debilitating physical symptoms including restlessness, high emotionality, and lowered mood [2]. Many studies have demonstrated that protracted morphine abstinence following spontaneous withdrawal causes emotion-related disorders in humans and corresponding behavioral responses in animals [2, 3]. Importantly, the depression and anxiety that occur during morphine addition and morphine abstinence often lead to a relapse in humans [4]. The depression and anxiety associated with morphine withdrawal can be alleviated by the administration of antidepressant or anxiolytic drugs such as fluoxetine or agmatine [5, 6]. However, most antidepressants are not very effective against the wide variety of
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