An understanding of the neurochemical changes occurring following exposure to psychostimulants such as cocaine is critical for the development of novel pharmacotherapies aimed at disrupting the addictive cycle. It is well established that the acute effects of cocaine associated with drug-induced blockade of dopamine (DA) reuptake processes occur in reward-related areas of the brain including the medial prefrontal cortex (mPFC). Considerable evidence has accumulated indicating that the interaction between DA, glutamate, and nitric oxide (NO) is likely to play a critical role in the neuroplastic changes associated with psychostimulant exposure. However, the potential impact of cocaine on NO synthase (NOS) activity in the mPFC has not been examined. In this study, NO efflux was measured in the mPFC of anesthetized male rats using a NO-selective electrochemical microsensor. Acute systemic administration of cocaine significantly increased NO efflux in the mPFC in a time-dependent manner. Similar injections using vehicle did not affect NO efflux. The facilitatory effect of cocaine on NO efflux was transient and reproducible. The signal was derived from neuronal sources of NO, because it was attenuated by systemic administration of the neuronal NO synthase inhibitor 7-nitroindazole. These studies support a role for prefrontal cortical NO signaling in cocaine-induced changes in neurotransmission in reward-related circuits involved in addiction.
Published 2008 Wiley-Liss, Inc.