Inhibition of neuronal nitric oxide synthase prevents alterations in medial prefrontal cortex excitability induced by repeated cocaine administration

FERNANDO J. NASIF; XIU-TI HU; OSCAR A RAMIREZ; MARIELA F. PÉREZ.

PSYCHOPHARMACOLOGY

SPRINGER

Año: 2011 vol. 218 p. 323 - 323

0033-3158

ationale: The medial prefrontal cortex (mPFC), a forebrain region thatregulates cognitive function and reward-motivated behaviors, has beenimplicated in the neuropathological mechanisms of drug addiction andwithdrawal. In cocaine-abstinent human addicts, neuronal activity of the mPFCis increased in response to cocaine re-exposure or drug-associated cues.Additionally, repeated cocaine exposure alters the membrane properties andion channel function of mPFC pyramidal neurons in drug-withdrawn rats,leading to an increased firing in response to excitatory stimuli. Nitric oxide (NO),a diffusible neuromodulator of neuronal excitability, may play a role in initiatingand maintaining behavioral effects of psychostimulants. However, the role ofNO in the mechanisms by which cocaine affects membrane excitability is notwell clarified.Objectives: In this study, we attempted to determine whether inhibition ofneuronal nitric oxide synthase (nNOS) altered the changes induced by repeatedcocaine exposure