Anxiety during nicotine withdrawal (NicW) is a key risk factor for smoking relapse. Semen Ziziphi Spinosae (SZS), which is a prototypical hypnotic-sedative herb in Oriental medicine, has been clinically used to treat insomnia and general anxiety disorders for thousands of years. Thus, the present study evaluated the effects of the aqueous extract of SZS (AESZS) on NicW-induced anxiety in male rats that received subcutaneous administrations of nicotine (Nic) (0.4 mg/kg, twice a day) for 7 d followed by 4 d of withdrawal. During NicW, the rats received four intragastric treatments of AESZS (60 mg/kg/d or 180 mg/kg/d). AESZS dose-dependently attenuated NicW-induced anxiety-like behaviors in the elevated plus maze (EPM) tests and 180 mg/kg/d AESZS inhibited NicW-induced increases in plasma corticosterone. Additionally, the protein and mRNA expressions of corticotropin-releasing factor (CRF) and CRF type 1 receptor (CRF1R) increased in the central nucleus of the amygdala (CeA) during NicW, but these changes were suppressed by 180 mg/kg/d AESZS. A post-AESZS infusion of CRF into the CeA abolished the attenuation of anxiety by AESZS and 180 mg/kg/d AESZS suppressed NicW-induced increases in norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the CeA. The present results suggest that AESZS ameliorated NicW-induced anxiety via improvements in CRF/CRF1R and noradrenergic signaling in the CeA.

No abstract

In a previous study, acupuncture at acupoint HT7 attenuated ethanol withdrawal-induced anxiety-like behavior in rats by normalizing amygdaloid catecholamines. In the present study, the involvement of amygdaloid corticotropin-releasing factor (CRF) in the anxiolytic effect of acupuncture was investigated during ethanol withdrawal. Rats were intraperitoneally treated with 3 g /kg/day of ethanol for 28 days, and the CRF mRNA levels in the central nucleus of the amygdala (CEA) were measured by using a RT-PCR analysis 72 hours after the last dose of ethanol. During ethanol withdrawal, the rats were bilaterally treated with acupuncture at acupoints HT7, PC6 or at a non-acupoint (Tail) for one min/day for three days. Also, rats were bilaterally injected with CRF into the CEA five minutes after the third acupuncture treatment, after which followed by the elevated-plus maze (EPM) test and the plasma corticosterone radioimmunoassay (RIA) were administered. The RT-PCR analysis showed a significant increase in the amygdaloid CRF mRNA levels in the ethanol-withdrawn rats compared with both the saline-treated rats and the rats treated with acupuncture at HT7, but neither acupuncture at PC6 nor acupuncture at a non-acupoint significantly inhibited the increased mRNA expression. The EPM test and the RIA also showed that the post-acupuncture infusion of CRF greatly reduced the anxiolytic effect of acupuncture at HT7. These results suggest that during ethanol withdrawal, the anxiolytic effect of acupuncture may be mediated through the modulation of amydaloid CRF during ethanol withdrawal.

Glycyrrhizae Radix modulates the neurochemical and locomotor alterations induced by acute psychostimulants in rodents via GABAb receptors. This study investigated the influence of methanol extract from Glycyrrhizae Radix (MEGR) on repeated methamphetamine- (METH-) induced locomotor sensitization and conditioned place preference (CPP). A cohort of rats was treated with METH (1 mg/kg/day) for 6 consecutive days, subjected to 6 days of withdrawal, and then challenged with the same dose of METH to induce locomotor sensitization; during the withdrawal period, the rats were administered MEGR (60 or 180 mg/kg/day). A separate cohort of rats was treated with either METH or saline every other day for 6 days in METH-paired or saline-paired chambers, respectively, to induce CPP. These rats were also administered MEGR (180 mg/kg) prior to every METH or CPP expression test. Pretreatment with MEGR (60 and 180 mg/kg/day) attenuated the expression of METH-induced locomotor sensitization dose-dependently, and 180 mg/kg MEGR significantly inhibited the development and expression of METH-induced CPP. Furthermore, administration of a selective GABAb receptor antagonist (SCH50911) prior to MEGR treatment effectively blocked the inhibitory effects of MEGR on locomotor sensitization, but not CPP. These results suggest that Glycyrrhizae Radix blocked repeated METH-induced behavioral changes via GABAb receptors.

No abstract

The current study investigated the effects of acupuncture at Zu-San-Li (ST36) on the hypothalamic-pituitary-adrenal axis during ethanol withdrawal in rats. Rats were intraperitoneally treated with 3 g/kg/day of ethanol or saline for 28 days. Following 24 hours of ethanol withdrawal, acupuncture was applied at bilateral ST36 points or non-acupoints (tail) for 1 minute. Plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay (RIA), and the corticotropin-releasing factor (CRF) protein levels in the paraventricular nucleus of the hypothalamus were also examined by RIA 20 minutes after the acupuncture treatment. RIA showed significantly increased plasma levels of CORT and ACTH in the ethanol-withdrawn rats compared with the saline-treated rats, which were inhibited significantly by the acupuncture at the acupoint ST36 but not at the non-acupoint. Additionally, ethanol withdrawal promoted CRF protein expressions in the paraventricular nucleus of the hypothalamus, which were also blocked by the acupuncture at ST36. These findings suggest that acupuncture at the specific acupoint ST36 can inhibit ethanol withdrawal-induced hyperactivation of hypothalamic-pituitary-adrenal axis, and it may be mediated via the modulation of hypothalamic CRF.

Acupuncture improves ethanol withdrawal-induced anxiety in rats in an acupoint-dependent manner. Thus, the present study investigated the effects of acupuncture on acute restraint stress- (ARS-) induced anxiety. Male rats were exposed to ARS for 3 h followed by acupuncture at either PC6 (Neiguan), HT7 (Shenmen), or a nonacupoint (tail) once a day for three consecutive days. Five minutes after the third acupuncture treatment, anxiety-like behavior was evaluated in an elevated plus maze (EPM). Additionally, plasma corticosterone (CORT) levels were measured by radioimmunoassay and the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the central nucleus of the amygdala (CeA) were determined using high-performance liquid chromatography. Acupuncture at PC6, but not HT7 or a nonacupoint, attenuated anxiety-like behavior, but this attenuation was abolished by a postacupunctural intra-CeA infusion of NE. Acupuncture at PC6 also reduced the oversecretion of plasma CORT and inhibited increases in amygdaloid NE and MHPG induced by ARS. Further, Western blot analyses and real-time polymerase chain reaction assays revealed that acupuncture at PC6 prevented ARS-induced enhancements in the protein and mRNA expressions of tyrosine hydroxylase in the CeA. These results suggest that acupuncture performed specifically at acupoint PC6 reduces ARS-induced anxiety-like behavior by dampening amygdaloid noradrenergic responses.

No abstract