Wild Ginseng Attenuates Anxiety- and Depression-Like Behaviors During Morphine Withdrawal

Abstract

The purpose of this study was to evaluate whether wild ginseng (WG) administration could attenuate anxiety-and depression-like behaviors and expression of corticotrophinreleasing factor (CRF) and neuropeptide Y (NPY) following withdrawal from repeated morphine administration in rats. Male rats were administered daily doses of WG (50, 100, or 200 mg/kg, i.p.) for 5 days, 30 min before morphine injection (40 mg/kg, s.c). The anxiety-and depression-like behavioral responses were measured 72 h after the last morphine injection using an elevated plus maze (EPM) and forced swimming test (FST), respectively. Changes in hypothalamic CRF and NPY expressions were also examined by analyzing their immunoreactivities in the hypothalamus. Daily administration of WG significantly reduced anxietyand depression-like behavior, and elicited the suppression of CRF expression and the stimulation of NPY expression in the hypothalamus. Our results demonstrated that WG extract might be effective at inhibiting the anxiety and depression responses due to morphine withdrawal by possibly modulating the hypothalamus CRF and NPY systems. Furthermore, these findings imply that WG extract can be used for developing new medication to cure or alleviate morphine withdrawal symptoms and to prevent relapses of morphine use.

Effects and mechanisms of ginseng and ginsenosides on cognition

“…Ginsenosides (i.p and p.o.) at a range of doses have also been shown to improve memory and learning impairment in models using morphine or ethanol to create deficits; taken together, these data suggest there may be multiple targets for the effects of ginsenosides on learning and memory.…”

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

“…In addition, morphine withdrawal-induced anxiety and depression-like behavior were effectively inhibited by wild ginseng extracts by modulating hypothalamic expression of CRF and NPY [133]. Moreover, the same group of researchers have reported that wild ginseng extracts effectively attenuated morphine withdrawal-induced behavioral sensitization along with modulation of c-Fos expression in nucleus accumbens and TH expression in ventral tegmental area suggesting the possible involvement of ginseng in the modulation of dopaminergic nervous system activity during morphine withdrawal [152].…”

“…Interestingly, the antidepressant-like activity was comparable to that of fluoxetine and S111 increased monoamine neurotransmitters in the brain and showed modest inhibitory effects against neurotransmitter reuptake in vitro . In contrast to fluoxetine, S111 inhibited oxidative stress and reduced serum corticosterone level in olfactory bulbectomized animals suggesting S111 modulates depression-like behavior by regulating multiple targets including both central and peripheral inflammation, regulation of hypothalamic corticotrophin-releasing factor (CRF) and Neuropeptide Y (NPY) expression and regulation of glucocorticoid receptor and BDNF expression as well as neurofilament-L in hippocampus [133-135,139]. Many of these results suggest that ginseng and ginsenosides regulate brain neurotransmitter turnover and hypothalamic- pituitary-adrenal axis.…”

Effect of Berberine on Depression- and Anxiety-Like Behaviors and Activation of the Noradrenergic System Induced by Development of Morphine Dependence in Rats

“…Many studies have demonstrated that morphine withdrawal causes depression- and anxiety-related disorders in humans and corresponding behavioral responses in animals [3,4]. Importantly, depression and anxiety that occur during morphine abstinence often lead to relapse to morphine use in humans [5]. Over the past several decades, several antidepressant classes [i.e., monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs)] have been developed and clinically used to treat psychiatric side-effects, including depression and anxiety, following morphine withdrawal [2].…”