Aim Posttraumatic nightmares are a core component of posttraumatic stress disorder （PTSD） and mechanistically linked to the development and maintenance of this disorder, but little is known about their mecha- nism. Methods We utilized a communication box to establish an animal model of physiological stress （foot-shock I FSI） and psychological stress （PS） to mimic the direct suffering and witnessing of traumatic events. Results Twenty-one days after traumatic stress, some of the experimental animals presented startled awakening （ i. e. , were startled awake by a supposed ＂nightmare＂） with different electroencephalographic spectra features. Our neuroan- atomical results showed that the secondary somatosensory cortex and primary auditory cortex may play an important role in remote traumatic memory retrieval in FS ＂nightmare＂ （FSN） rats, whereas the temporal association cortex may play an important role in PS ＂nightmare＂ （PSN） rats. The FSN and PSN groups possessed common emotion evocation circuits, including activation of the amygdala and inactivation of the infralimbic prefrontal cortex and ven- tral anterior cingulate cortex. The decreased activity of the granular and dysgranular insular cortex was only oh-served in PSN rats. Conclusion The present results imply that different types of stress may cause PTSD-like ＂nightmares＂ in rodents and identified the possible neurocircuitry of memory retrieval and emotion evocation.
OBJECTIVE Dorsal raphe nucleus(DRN) is the largest single collection of neurons containing5-HT in the entire brain and particularly attractive in a wide variety of complex physiological and behavioral processes,such as sleep-wake regulation. Calmodulin dependent kinaseⅡ(CaMKⅡ) and protein kinase C(PKC)are important signal-transducing molecules activated by Ca^(2+). Since the Ca^(2+)modulation in DRN plays an important role in sleep-wake regulation,it should be presumed that the intracellular CaMKⅡ/PKC signaling in DRN may be involved in the regulation of sleep-wake. METHODS The polysomnogram consisting of EEG and EMG was recorded for analyzing sleep architecture. Immunohistochemisrty and Western-blotting methods were used in this study to investigate the roles of Ca^(2+),CaMKⅡ and PKC in sleep-wake regulation in rat DRN. RESULTS Ca^(2+)in the DRN exert arousal effects by reducing the NREMs,SWS and REMs via up-regulating serotonergic functions and activating CaMK Ⅱ-PKC.However,inhibition of PKC leads to significant promotion of total sleep time especial y the NREM sleep,but there were no changes in sleep parameters after the inhibition of CaMKⅡ by its inhibitor KN-93 in DRN.CONCLUSION The molecular,pharmacological,and behavioral findings of this study demonstrate a novel wake promoting and sleep-suppressing role for the Ca^(2+)/CaMK Ⅱ/PKC signaling pathway in DRN. Abnormalities in CaMK Ⅱ are found in patients with several neurological disorders that are associated with disturbed sleep,such as schizophrenia,depression,and Alzheimer′s disease. Several psychotropic drugs modulate CaMK Ⅱ activity. In addition,PKC is a cellular target of most current mood stabilizing and anti-manic agents and involved in bipolar disorder. The data of the present study raise the question whether PKC or CaMKⅡ modulations may also be effective on the sleep disorders or the mood disorders associated with sleep disorders.
OBJECTIVE Bisbenzylisoquinoline(BBI)alkaloids have extensive pharmacological functions.The aim of this study was to investigate the mechanisms underlying the antidepressant-like action of 7-O-ethylfangchinoline(YH-200)in mice.METHODS Male ICR mice were used in the forced swimming(FST)and tail suspension tests(TST).RESULTS YH-200(60mg·kg-1,ig)decreased the immobility time in FST and TST,and prolonged the latency to immobility in FST.YH-200 revealed more potent anti-immobility activity than its BBI derivative tetrandrine.In addition,the pretreatment of mice with prazosin(1mg·kg-1,ip,anα1-adrenoceptor antagonist),propranolol(2 mg·kg-1,ip,a nonselectiveβ-adrenoceptor antagonist),SCH23390(0.05mg·kg-1,ip,a dopamine D1/D5 receptor antagonist),haloperidol(0.2mg·kg-1,ip,a dopamine D2/D3 receptor antagonist)and NBQX(10mg·kg-1,ip,an AMPA receptor antagonist)prevented the antidepressant-like effect of YH-200(60mg·kg-1,ig)in FST.Besides that,the pretreatment of mice with yohimbine(1mg·kg-1,ip,an α2 adrenoceptor antagonist)augmented the antidepressant-like effect of YH-200(30mg·kg-1,ig)in FST.After 14 dadministration,YH-200(30 and 60mg·kg-1,ig)did not develop drug resistance,but the potency was strengthened,meanwhile,it did not influence the changes in mice body weight.CONCLUSION YH-200 may possess the therapeutic potential for the treatment of depression via the multi-targets including the noradrenergic(α1,α2 and β-adrenoceptors),dopaminergic(D1/D5 and D2/D3receptors)and AMPAergic systems.
