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Among the most powerful analgesics, morphine is widely used in clinic.However, they are potentially extremely addictive thereby limiting their medical use.It is believed that morphine inhibits the GABAergic neurons in the ventral tegmental area (VTA), thereby disinhibits the dopamine neurons, causing reward and leading to the desire for drugs.Morphine is usually applied as the agonist of mu-opioid receptor (MOR).Interestingly, no intense addiction is triggered by some agonists of MOR, such as methadone and DAMGO.Our research was focused on the effect and mechanism of morphine in VTA, using patch clamp recording inhibitory postsynaptic current (IPSC)on dopamine neurons.The results suggested the agonist of delta-opioid receptor (DOR) increased GABA release in slices incubated with morphine not DAMGO.However, perfusing morphine and DAMGO both inhibited GABA release via activating MOR on GABAergic terminals.Further we noticed that protein kinase C (PKC) was involved in inhibition of GABA by perfusing DAMGO, but not morphine.These different effects between morphine and DAMGO may provide foundational contribution to addiction.