Acute cocaine administration depresses cortical activity.

Psychostimulants, when administered acutely, produce significant deficits in cognitive tasks. Indeed, there is considerable evidence that acute administration of cocaine alters cellular processes at the level of the nucleus accumbens and the ventral tegmental area (VTA). However, there have been few studies that explore the acute effects of cocaine in the prefrontal cortex (PFC). Here we report that acute cocaine administration in vivo evokes a prolonged membrane depolarization, decreases cortical spontaneous firing, compromises spontaneous membrane bistability, and blunts the VTA-evoked responses in the PFC. Moreover, acute cocaine administration decreases the amplitude of the EPSP-IPSP sequence that precedes the initiation of the Up states in the PFC, therefore compromising the driving force of cortical bistability and thereby cortical excitability.