Abstract: The disclosure discloses a use of cyclic adenosine monophosphate (cAMP), derivative or prodrug thereof in preparation of drug for preventing and/or treating depression. Using the established model of depressed mice caused by social defeat stress, cAMP is intraperitoneally injected upon constructing the model or directly injected into the nucleus accumbens brain region of depressed mice after modeling, which can significantly improve the depression-like behavior of mice. The disclosure discloses the prevention and treatment effect of cAMP on depression, and provides a candidate drug with new mechanism for clinical prevention and treatment of depression.