Delta-9-tetrahydrocannabinol (THC) is the main psychoactive component of the Cannabis plant. The molecular mechanisms by which THC acts in the brain and their cross-talk with other endogenous neuroendocrine systems are just beginning to be investigated. Here, we evaluated the neuroanatomical and behavioral effects of the central treatment with THC in mice. First, we administered intracerebroventricularly (ICV) 5 mg of THC to wild-type male mice and assessed the induction of the marker of neuronal activation c-Fos 2-h after treatment as compared to vehicle-treated mice (n=4 and 3, respectively). We found that THC induced an increase of the number of C-Fos positive cells the supramammillary nucleus (SuM), whereas it did not change the number of C-Fos positive cells in other brain areas, such as ventral tegmental area (VTA), nucleus accumbens (Acb) and LHA. In parallel, we assessed acute and overnight food intake as well as on locomotor activity and conditioned place preference, and failed to find THC-induced effects. Thus, our preliminary data indicates that ICV administration of 5 mg of THC induces SuM activation without behavioral effects unmasked with the tested approaches. We have set up experimental conditions in mice to uncover central effects of THC, we hope to improve such experimental conditions to now investigate novel aspects of the THC action in the brain.