Inhibition of neuronal nitric oxide synthase prevents alterations in

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

PSYCHOPHARMACOLOGY

SPRINGER

Año: 2010

0033-3158

Rationale The medial prefrontal cortex (mPFC), a forebrain region that regulates cognitive function and reward-motivated behaviors, has been implicated in the neuropathological mechanisms of drug addiction and withdrawal. In cocaine-abstinent human addicts, neuronal activity of the mPFC is increased in response to cocaine re-exposure or drug-associated cues. Additionally, repeated cocaine exposure alters the membrane properties and ion channel function of mPFC pyramidal neurons in drug-withdrawn rats, leading to an increased firing in response to excitatory stimuli.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 initiating and maintaining behavioral effects of psychostimulants. However, the role of NO in the mechanisms by which cocaine affects membrane excitability is not well clarified. Objectives In this study, we attempted to determine whether inhibition of neuronal nitric oxide synthase (nNOS) altered the changes induced by repeated cocaine exposure and withdrawal.