Steroid hormones participate in a wide variety of biological processes. The major steroid hormone in insects is ecdysone, which executes its functions mainly through "genomic" actions by activating nuclear hormone receptors to regulate transcription of target genes. Recently, a novel G-protein coupled receptor (GPCR), DopEcR, has been identified in Drosophila and shown to mediate nuclear receptor-independent, "non-genomic" actions of ecdysone in the heterologous cell expression systems. However, the in vivo functional significance and molecular mechanisms of such unconventional ecdysone signaling still remain elusive. Here we have found that DopEcR hypomorphic mutants exhibit abnormally slow habituation of the giant fiber pathway and have a defect in experience-dependent courtship suppression. Intriguingly, these abnormalities in non-associative and associative learning resemble those of loss-of-function mutants for rutabaga (rut) that encodes Ca2+/CaM-dependent adenylyl cyclase. More importantly, genetic or pharmacological potentiation of DopEcR-mediated ecdysone signaling restored the associative learning defect in rut mutants, suggesting that DopEcR-mediated ecdysone signaling positively regulates cAMP levels. Consistent with this idea, peroral application of 20-hydroxyecdysone, an active metabolite of ecdysone, induced a rapid, DopEcR-dependent increase in cAMP levels in the mushroom bodies, a memory center of the fly brain. Taken together, our study has demonstrated that non-genomic ecdysone actions mediate novel GPCR-cAMP signaling and play critical roles in neural plasticity, providing a new insight into the unconventional steroid signaling.