Rebound depolarization (RD) is a form of membrane depolarization triggered in some neurons following hyperpolarization. Typically, a series of action potentials are evoked during RD plateau. RD converts an inhibitory signal arriving to the neuron into an excitation signal, which is subsequently synaptically transmitted to other cells. The nature of RD in cortical neurons has been tested for several years without satisfactory explanation. The aim of our study was to evaluate the influence of adrenergic receptors activation in RD generation. Alpha-1, alpha-2, and beta-receptors have been tested. Experiments were performed on layer V medial prefrontal cortex (mPFC) pyramidal neurons in slices obtained from adult (58-65-day-old) male rats. Recordings of membrane potential were performed in a whole-cell current-clamp configuration in the presence of voltage-gated sodium channels blocker (TTX), glutamatergic and GABAergic blockers (DNQX, DL-AP5, picrotoxin) in extracellular solution. Therefore, the tested neurons were synaptically isolated. Our results show that adrenergic receptors stimulation by noradrenaline (NA), cirazoline (alpha-1-adrenoceptor agonist) and isoproterenol (beta-adrenoceptor agonist) evoked RD. While clonidine (alpha-2-adrenoceptor agonist) was applied to the extracellular solution, the membrane potential level did not significantly change. The obtained results suggest that RD in layer V mPFC pyramidal neurons is evoked by the activation of alpha-1 and beta-adrenoceptors, while the activation of alpha-2-adrenoceptor do not arouse RD.The study was supported by the Medical University of Warsaw (grant number: FW3/2/F/MG/N/20).