Stimulation of prefrontal cortex at physiologically relevant frequencies inhibits dopamine release in the nucleus accumbens

The prefrontal cortex (PFC) is thought to provide an excitatory influence o n the output of mesoaccumbens dopamine neurons. The evidence for this influ ence primarily arises from findings in the rat that chemical or high-intens ity and high-frequency (60-200Hz) electrical stimulations of PFC increase b urst activity of midbrain dopamine neurons, and augment terminal release of dopamine in the nucleus accumbens. However, PFC neurons in animals that ar e engaged in PFC-dependent cognitive tasks increase their firing frequency from a baseline of 1-3 Hz to 7-10 Hz, suggesting that the commonly used hig h-frequency stimulation parameters of the PFC may not be relevant to the be havioral states that are associated with PFC activation. We investigated th e influence of PFC activation at lower physiologically relevant frequencies on the release of dopamine in the nucleus accumbens. Using rapid (5-min) m icrodialysis measures of extracellular dopamine in the nucleus accumbens, w e found that although PFC stimulation at 60 Hz produces the expected increa ses in accumbal dopamine release, the same amplitude of PFC stimulation at 10 Hz significantly decreased these levels. These results indicate that act ivation of PFC, at frequencies that are associated with increased cognitive demand on this region, inhibits the mesoaccumbens dopamine system.