Effects of yohimbine on norepinephrine release by locus coeruleus in stressed rats

Abstract

Objective To study the cellular and molecular modulation mechanisms of norepinephrine (NE) release in hypothalamus induced by electrical stimulation in locus coeruleus(LC) in the rat model of depression-like behavior . Methods The depression-like behavior model was established by combining separation and chronic unpredictable stress stimulations.After the model establishment, behavior tests were used to verify the success of modeling. NE release in the hypothalamus induced by electrical stimulation in LC was studied in real time and NE signal was recorded with carbon fiber electrode. The peak value, the time to peak and half-life period of NE signal in both group rats were measured and analysed. Results The bodyweight, score of open-field test, percentage of sucrose preference of model group rats((263.9±16.4)g, (19.4±7.9), (44.3±10.8)%) were significantly lower than those((314.3±24.3)g, ( 53.3±19.0), ( 60.6±13.3)%) of control group(P<0.01). The peak value of NE signal in the hypothalamus induced by electrical stimulation in locus coeruleus in depression-like behavior model rats((176.9±50.4) pA)was less than that((361.6±88.6) pA )in control group(P<0.01), and the time to peak of NE signal was also shortened in depression-like behavior model group rats(P<0.05). Intraperitoneal injection of yohimbine (3 mg/kg) potentiated electrical stimulation induced NE release in depression-like behavior model rats but not in control group. Conclusion The chronic unpredictable stresses attenuate the secretion of NE in the hypothalamus induced by electrical stimulation in LC in rats. Yohimbine, a presynaptic α2 receptor antagonist, increased NE release in hypothalamus in depression-like behavior model rats. These findings suggest that the LC projects functionally to the hypothalamus and the projection may contribute to the pathogenesis of depression. Key words: Chronic unpredictable stress; Rats; Locus coeruleus; Hypothalamus; Yohimbine