Abnormal activity of the DA system has been implicated in neurological and psychiatric disorders, such as Parkinson’s disease, schizophrenia, bipolar disorder and attention deficit hyperactivity disorder. Thus, the study of DA receptor-mediated intracellular signal transduction has been a primary approach toward understanding the physiological functions as well as pathophysiological aspects of DA-related cellular responses. D1- and D2-class DA receptor subtypes positively and negatively regulate adenylyl cyclase, respectively, and D2 receptors are coupled to phospholipase C. Although the contribution of D1 receptors is unclear, stimulation of D2 receptors can increase intracellular Ca2+ concentrations by mobilization of Ca2+ from inositol-1,4,5-trisphosphate-sensitive stores, followed by activation of ryanodine-sensitive Ca2+ pools. Increased in intracellular free calcium concentration ([Ca2+]i) seem to be mediated by interaction of DA receptors with DA receptor interacting proteins, such as neuronal calcium sensor-1 or calcyon. Ca2+-dependent cellular responses are also mediated by calcineurin to dephosphorylate DPADPP. Therefore, it is of interest to determine any crosstalk between Ca2+ and other second messengers, such as cyclic ADP-ribose (cADPR), in the downstream signalling of DA receptors. The mTOR pathway has emerged as a regulator of neuroplasticity in the central nervous system. It has been shown that administration of L-DOPA in a mouse model of Parkinsonism leads to dopamine D1 receptor-mediated activation of the mTOR complex 1 (mTORC1), which has been implicated in several forms of synaptic plasticity. The L-DOPA-mediated activation of mTORC1 persisted in mice that developed dyskinesia. Moreover, the mTORC1 inhibitor rapamycin prevented the development of dyskinesia without affecting the therapeutic efficacy of L-DOPA. Thus, the mTORC1 signalling cascade represents a promising target for the design of anti-parkinsonian therapies.Here, we addressed whether cADPR plays a role as a second messenger and modulator of the mTOR pathway downstream of DA receptors through FKBP12.6 or FKBP12 in the rodent striatum. For this purpose, ADP-ribosyl cyclase activity was measured in the crude membrane fractions of rats and mice in the presence or absence of DA, and phosphorylation of S6K in whole homogenates of the isolated mouse striatum after incubation with or without cADPR was measured. mTOR1 activates the S6 K, which is responsible for phosphorylation of the ribosomal protein S6, a component of the 40S ribosomal subunit. cADPR significantly decreased in S6K phosphorylation, which was reversed by the prior administration of 8-bromo-cADPR, a cADPR antagonist. These results suggest that the abundant cADPR seems to be an intrinsic regulator of the mTOR signal in the adult striatum.