Amygdaloid Corticotropin-releasing Factor is Involved in the Anxiolytic Effect of Acupuncture during Ethanol Withdrawal in Rats

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 The RT-PCR analysis showed a significant increase in the amygdaloid CRF mRNA levels in the ethanol-withdrawn rats compared with both the saline-treated rats and the rats treated with acupuncture at HT7, but neither acupuncture at PC6 nor acupuncture at a non-acupoint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.

Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic–Pituitary–Adrenal Axis During Ethanol Withdrawal

“…that the selective NEergic alpha1 receptor antagonist prazosin concurrently blocks the anxiety and the increase in ethanol intake induced by EW, reflecting the positive correlation between the NEergic system and the HPA in the regulation of ethanol consumption. The simultaneous hyperactivation of NE and CRF in the central nervous system during EW has also been demonstrated in our previous studies showing elevated activation in both amygdaloid NE and CRF during EW [8,9]. Additionally, in a recently published study, we also reported increased CRF protein expression in the rat PVN 24 hours after cessation of ethanol administration [12].…”

“…Acute ethanol increases hypothalamic NE neosynthesis [4] and plasma corticosterone (CORT) secretion [5], and chronic ethanol can produce elevated blood glucocorticoid levels as well as increased activity in the sympathetic nervous system [6]. Dar and Wooles [7] have reported increased hypothalamic NE concentrations in EW mice, and we have also demonstrated that EW raises amygdaloid NE and CRF mRNA levels in rats [8,9].…”

Aqueous Extract of Semen Ziziphi Spinosae Exerts Anxiolytic Effects during Nicotine Withdrawal via Improvement of Amygdaloid CRF/CRF1R Signaling

“…Amygdaloid CRF1R, but not CRF2R, mediates anxiety-like behavior in mouse EPM tests [ 36 , 37 ] and activation of CRF1R, but not CRF2R, in the CeA affects ethanol withdrawal-induced anxiety in rats [ 38 ]. A previous study by our research group revealed that ethanol withdrawal increases CRF mRNA expressions in the rat CeA [ 39 ]. In the present study, real-time PCR and Western blot analyses displayed increased protein and mRNA expressions for both CRF and CRF1R in the CeA of rats undergoing NicW, which are consistent with the studies done by others showing that NicW robustly increases the mRNA levels of CRF and CRF1R in the CeA [ 40 ].…”

“…Ultrastructural and pharmacological analyses have revealed that CRF neurons in the CeA are targeted by noradrenergic afferents [ 41 ], that NE is a secretagogue of CRF, and that the activation of β -adrenergic receptors appears to stimulate CRF gene expression in the extended amygdala [ 15 , 42 ]. Our previous studies have shown ethanol withdrawal simultaneously elevates noradrenergic transmission and CRF mRNA expression in the CeA [ 17 , 39 ]; in addition, the studies done by others have also identified the parallel functional promotion of the noradrenergic and CRFergic systems in the CeA following the cessation of the chronic abuse of drugs [ 43 , 44 ]. Accordingly, in the present study, NicW significantly increased both NE and MHPG levels in the CeA, whereas the administration of 180 mg/kg/d AESZS prevented these increases.…”

Korean Red Ginseng attenuates anxiety-like behavior during ethanol withdrawal in rats

“…and stainless steel guide cannulae (15 mm; 23 gauge) were bilaterally implanted into the amygdala using a stereotaxic instrument with the cannula tips 2 mm above the CeA using the same coordinates described above [15] . The guide cannulae were secured in place using two small stainless steel screws anchored to the skull with dental acrylic cement [16] . Animals were allowed 7 d of recovery following the surgery.…”