H_1 and H_2 receptors in the locus ceruleus are involved in the intracere-broventricular histamine-induced carotid sinus baroreceptor reflex reset-ting in rats

Objective To investigate the role of H1 and H2 receptors in the locus ceruleus （LC） in carotid sinus baroreceptor reflex （CSR） resetting induced by intracerebroventricular （i.c.v.） injection of histamine （HA）. Methods The left and right carotid sinus regions were isolated from the systemic circulation in 18 male Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure （ISP） was altered in a stepwise manner in vivo. ISP-mean arterial pressure （MAP） relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CSR performance induced by i.c.v. HA and the effects of pretreatment with H1 or H2 receptors selective antagonist, chlorpheniramine （CHL） or cimetidine （CIM） into the LC, on the responses of CSR to HA were examined. Results I.c.v. HA （100 ng in 5 μl） significantly shifted the ISP-MAP relationship curve upwards （P 〈 0.05） and obviously decreased the value of the reflex parameters such as MAP range and maximum gain （P 〈 0.05）, but increased the threshold pressure, saturation pressure and ISP at maximum gain （P 〈 0.05）. The pretreatment with CHL （0.5 μg in 1 μl） or CIM （1.5 μg in 1 μl） into the LC could obviously attenuate the changes mentioned above in CSR performance induced by HA, but the alleviative effect of CIM was less remarkable than that of CHL （P 〈 0.05）. Respective microinjection of CHL or CIM alone into the LC with the corresponding dose and volume did not change CSR performance significantly （P 〉 0.05）. Conclusion Intracerebroventricular administration of HA results in a rapid resetting of CSR and a decrease in reflex sensitivity, and the responses of CSR to HA may be mediated, at least in part, by H1 and H2 receptors activities in the LC, especially by H1 receptors. Moreover, the effects of the central HA on CSR might be related to a histaminergic descending pathway from the hypothalamus to LC.

Effects of acetylcholine injection on electric activities of pain-related neurons in the locus ceruleus of healthy rats

BACKGROUND： A large number of investigations have shown that acetylcholine （ACh） and the nucleus locus coeruleus （LC） play an important role in the modulation of pain in rats; however, there is no concrete evidence addressing the relationship between ACh injection into the LC and the electrical activities of pain-related neurons in the LC of healthy rats. OBJECTIVE： To study changes in the discharge of pain-related neurons in the LC following injection of ACh, or its M receptor antagonist, atropine, and to investigate the role of ACh and the LC in the pain signaling pathway. DESIGN, TIME AND SETTING： A randomized, controlled, neuroelectrophysiological animal experiment was performed from November 2007 to December 2008, in the Physiological Laboratory of Harbin Medical University, China. MATERIALS： Acetylcholine chloride was obtained from Shanghai San＇aisi Reagent Co., Ltd., China atropine was purchased from Tianjin Jinyao Amino Acid Co., Ltd., China. METHODS： This study was divided into two sections as follows： （1） 46 adult Wistar rats were randomly assigned into an ACh group and a control group, with 23 rats in each. （2） 34 adult Wistar rats were randomly assigned to an atropine group and a control group, with 17 rats in each. The sciatic nerve was stimulated by a series of electrical impulses, serving as peripheral noxious stimuli. Electrical changes in pain-related neurons in the LC were measured by glass microelectrodes. The LC of rats in the ACh and atropine groups were injected with 2 μg/μL ACh or 0.5 μg/μL atropine, respectively, in 1 μL volume. Rats in the control groups received injection of 1 pL physiological saline within 4 minutes. MAIN OUTCOME MEASURES： To measure the net increase in the discharge value, latency and complete inhibitory duration of pain-related neurons before and after administration of ACh or atropine. RESULTS： The injection of ACh into the LC increased the pain-evoked discharge frequency and shortened the latency of the pain-excitation neurons. It decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of pain-inhibition neurons. Injection of atropine into LC blocked the effects of ACh. CONCLUSION： ACh strengthened the response of pain-related neurons in LC of rats to noxious stimulation, exhibiting the effects of facilitated pain. This indicates that ACh and LC play an important role in the modulation of algesia.