Corticotrophin-releasing hormone neurons in the central amygdala mediate morphine withdrawal-induced negative emotions / 生理学报

ABSTRACT

Drugs of abuse leads to adaptive changes in the brain stress system, and produces negative affective states including aversion and anxiety after drug use is terminated. Corticotrophin-releasing hormone (CRH) is the main transmitter in control of response to stressors and is neuronal enriched in the central amygdala (CeA), a sub-region of the extended amygdala playing an important role in integrating emotional information and modulating stress response. The effect of CRH neurons in CeA on the negative emotions on morphine naïve and withdrawal mice is unclear. Thus, we utilized CRH-Cre transgenic mice injected with AAV-mediated Designer Receptors Exclusively Activated By Designer Drugs (DREADDs) to chemogenetically manipulate CRH neurons in CeA. And methods of behavior analysis, including conditioned place aversion (CPA), elevated plus maze and locomotor activity tests, were used to investigate morphine withdrawal-induced negative emotions in mice. The results showed that, inhibiting CRH neurons of CeA decreased the formation of morphine withdrawal-induced CPA, as well as the anxiety level of CRH-Cre mice. Furthermore, specifically activating CRH neurons in CeA evoked CPA and anxiety of morphine naïve mice. Neither inhibiting nor activating CRH neurons had effects on their locomotor activity. These results suggest that CRH neurons in CeA are involved in the mediation of morphine withdrawal-induced negative emotion in mice, providing a theoretical basis for drug addiction and relapse mechanism.