Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex

A dynamic interaction between the prefrontal cortex (PFC), amygdala, and nu cleus accumbens (NAc) may be fundamental to regulation of goal-directed beh avior by affective and cognitive processes. This study demonstrates that a mechanism for this triadic relationship is an inhibitory control by prefron tal cortex on accumbal dopamine release during amygdala activation. In free ly moving rats, microstimulation of basolateral amygdala at intensities tha t produced mild behavioral activation produced an expected rapid increase i n glutamate efflux in the prefrontal cortex and the nucleus accumbens shell region of the ventral striatum. However, during the stimulation, dopamine release increased only in the prefrontal cortex, not in the nucleus accumbe ns. An increase in accumbal dopamine release was observed during the stimul ation if glutamate activation in the prefrontal cortex was inhibited at eit her presynaptic or postsynaptic levels. Some behaviors expressed during the stimulation were intensified in animals in which prefrontal cortex glutama te activation was blocked. In addition, these animals continued to express stimulus-induced behaviors after the termination of stimulation, whereas no rmal poststimulus behaviors such as ambulation and grooming were not displa yed as frequently. Considering that dopamine neurotransmission in the nucle us accumbens is thought to play an integral role in goal-directed motor beh avior, these findings suggest that the prefrontal cortex influences the beh avioral impact of amygdala activation via a concomitant active suppression of accumbal dopamine release. Absence of this cortical influence appears to result in an aberrant pattern of behavioral expression in response to amyg dala activation, including behavioral perseveration after stimulus terminat ion.