The regulatory role of the hypothalamic lateral area-ventral tegmental nucleus melanin-concentrating hormone neural pathway in anxiety-like behavior in mice
Objective To explore the regulatory role of the melanin-concentrating hormone(MCH)neural pathway from the lateral hypothalamus(LHA)to the nucleus accumbens(NAc)in modulating anxie-ty-like behavior in mice.Methods Totally 37 male SPF-grade C57BL/6J mice,aged 6 to 8 weeks and weighed 18-22 g,were used for the following experiment:(1)Five mice received an injection of Fluoro-Gold(FG)into the NAc,followed by retrograde tracing combined with immunofluorescence staining after one week to observe the coexistence of FG and MCH immunopositive neurons in the LHA.(2)Thirty-two mice were in-jected with adeno-associated virus which could activate the MCH neurons into the LHA.After two weeks,they were randomly divided into four groups and received different drug injections:normal saline(NS,intraperito-neal injection)+NS(1.5 μL,injection in the NAc)group,NS(intraperitoned injection)+SNAP94847(SNAP,2 mg/mL,1.5 μL,injection in the NAc)group,chlorprothixene N-oxide(CNO,O.15 mg/kg,intra-peritoned injection)+NS(1.5 μL,injection in the NAc)group,and CNO(intraperitoned injection)+SNAP(1.5 μL injection in the NAc)group,and the SNAP94847 was an antagonist for MCH typel receptor.The open field test(OFT),elevated plus maze(EPM),and marble burial test(MBT)were employed to as-sess the impact of chemogenetic activation of MCH neurons on anxiety-related behavior in mice.Results(1)The results of FG retrograde tracing combined with immunofluorescence histochemistry showed that MCH neurons in the LHA project their neural fibers to NAc neurons.(2)In the chemogenetic experiment,there was no significant interaction effect between CNO and SNAP in terms of the duration of stay(Finteraction=2.899,P＞0.05)and the distance moved(Finteraction=1.603,P＞0.05)in the central area during OFT experiments.However,the main effects of both CNO and SNAP intervention were significant in the dura-tion of stay(FCNO=6.767,FSNAP=7.656,both P＜0.05)and the distance moved(FCNO=12.480,FSNAP=7.999,both P＜0.01)in the central area.Compared to the NS+NS group,mice in the CNO+NS group exhibi-ted a shortened duration of stay((89.00±19.16)s,(63.75±13.58)s,P＜0.05)and a decrease in distance moved((593.79±108.18)cm,(426.81±66.14)cm,P＜0.05)in the central area.In contrast,mice in the CNO+SNAP group had an extended duration of stay((87.38±16.57)s)and an increase in distance moved((569.27±73.20)cm)in the central area compared to the CNO+NS group.There was no significant inter-action effect between CNO and SNAP in the number of entries(Finteraction=2.79,P＞0.05)and the dwell time(Finteraction=2.871,P＞0.05)into the open arms of EPM experiments.However,the main effects of both CNO and SNAP interventions in the number of entries(FCNO=10.43,P＜0.01;FSNAP=4.96,P＜0.05)and the dwell time(FCNO=5.232,FSNAP=7.597,both P＜0.05)into the open arms were significant.Compared to the NS+NS group,mice in the CNO+NS group showed a decrease in the number of entries((13.13±3.36),(7.63±3.70),P＜0.01)and a decrease in open arm dwell time((37.68±11.37)s,(22.98±7.00)s,P＜0.05)into the open arms.The CNO+SNAP group had an increased number of entries(12.00±3.02)and an increased dwell time((39.41±10.58)s)into the open arms compared to the CNO+NS group(both P＜0.05).There was no significant interaction effect between CNO and SNAP in the MBT experiment(Finteraction=2.746,P＞0.05).However,the main effects of both CNO and SNAP interventions were significant(FCNO=8.125,P＜0.01;FSNAP=5.383,P＜0.05).Compared to the NS+NS group,the number of buried beads increased in the CNO+NS group((16.13±2.10),(11.88±3.23),P＜0.05).Conversely,the number of buried beads decreased in the CNO+SNAP group compared to the CNO+NS group((12.38±2.33),(16.13±2.10),P＜0.05).Conclusion Enhanced activity in the MCHergic neural pathway from LHA to NAc can promote anxiety-like behavior in mice,providing new insights into the mechanisms underlying anxiety.
Lateral hypothalamusNucleus accumbensMelanin-concentrating hormoneAn-tagonist for melanin-concentrating hormone receptorSNAP94847AnxietyMouse
NETL
NSTL
万方数据
