| Objective：To study the cellular and receptor mechanism of norepinephrine(NE) secretion in hypothalamus followed by electrical stimulation in locus coeruleus(LC) in the rat model of chronic unpredictable stress. The release of NE inhypothalamus was detected using carbon fiber electrode. The effects of adrenergicreceptor antagonist yohimbine and propranolol on NE secretion were further studied toexplore the mechanisms of adrenergic receptor on locus coeruleus secretion.Methods： Male clean grade Wistar rats (180-200g) were divided into highscore group and low score group by open-field test before modeling. There were10ratsof each group. The depression model was established by combining separation andchronic unpredictable stress stimulations in low score group rats. Open field test scores,pecentage of sucrose consumption, body weight, blood pressure and heart rate weremonitored from the beginning to the end of modeling once a week. NE release in thehypothalamus by electrical stimulation in LC was studied and NE signal was recordedby carbon fiber electrode in both group rats. The peak value, the time to peak andhalf-decay time of NE signal in both group rats were analysed. α2-adrenergic receptorantagonist yohimbine and β-adrenergic receptor antagonist propranolol wereintraperitoneally administrated in both group rats respectively to observe the effects ofadrenergic receptor on NE secretion.Results：The body weight of model group rats increased more slowly than control group （267.45±18.0g,n=20vs326.3±28.3g，n=20, P＜0.01）；The open field test scores ofmodel group rats were significantly lower than control group(27.4±15.8,n=20vs61.1±17.7,n=20, P＜0.01)；The percentage of sucrose preference of model group rats weresignificantly lower than control group (2.2±1.2g,n=20vs5.0±2.6,n=20, P＜0.01).No significant difference of blood pressure or heart rate was seen between two grouprats.The peak value(206.2±49.7pA,n=19vs345.5±72.7pA,n=19, P＜0.01) and thetime to peak(2.0±0.4s,n=19vs2.5±0.6s,n=19, P＜0.05) of NE signal in thehypothalamic followed by electrical stimulation in locus coeruleus in chronicunpredictable stress model rats were less than those in controls. There were nosignificant difference of the half-decay time of NE signal between two group rats.Intraperitoneal injection of yohimbine (3mg/kg) potentiated the peak value(353.9±96.7pA,n=9vs176.9±50.4pA,n=9, P＜0.01)and the time to peak(2.1±0.2s,n=9vs1.8±0.3s,n=9, P＜0.05) of NE release in the hypothalamus induced by electricalstimulation in locus coeruleus unpredictable stress model rats. The peak value and timeto peak of NE release were also increased in control group rats after yohimbineadministration, but this increasement has no significant difference.Intraperitoneal injection of propranolol (5mg/kg) enhanced the peak value（293±66.4,n=10vs232.5±32.5,n=10, P＜0.01）of electrical stimulation induced in locuscoeruleus secretion of NE in the hypothalamus in unpredictable stress model rats. Thepeak value of NE release was also increased in control group rats after propranololadministration, but this increasement also has no significant difference.Conclusions：1) The chronic unpredictable stresses induced depression-like behaviors in rat.2) Electrical stimulation induced locus coeruleus secretion of NE in thehypothalamus was decreased in the chronic unpredictable stresses model rats.3) Yohimbine, an α2adrenergic receptor antagonist, increased the NE release in hypothalamus in chronic unpredictable stress model rats.4) Propranolol, a βadrenergic receptor antagonist, increased the NE release inhypothalamus in chronic unpredictable stress model rats.5) The nerve fiber projection of LC to the hypothalamus functionally contribtes tothe pathogenesis of chronic unpredictable stresses induced depression-likebehaviors. |
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