Activation of feeding-related neural circuitry after unilateral injections of muscimol into the nucleus accumbens shell

Chemical inhibition of neurons in the nucleus accumbens shell (AcbSh) elicits intense, behaviorally specific, feeding in satiated rats. We have demonstrated previously that this treatment activates a number of brain regions, most significantly the lateral hypothalamus (LH). This activation could be elicited through a direct neural connection with the AcbSh or secondarily through changes in autonomic activity, stress, or circulating levels of orexigenic or satiety factors. In the present study, we used the immunohistochemical localization of Fos protein to map neuronal activation after unilateral muscimol injections into the AcbSh to determine whether AcbSh-mediated Fos expression remains lateralized in the circuit and whether secondary systemic changes in the rat can be excluded as primary factors in the activation of downstream component nuclei. Rats receiving only saline injections exhibited very little Fos immunoreactivity. In contrast, unilateral injections of muscimol into the AcbSh consistently increased Fos expression in several brain regions. Three distinct patterns of expression were observed. Fos synthesis in the LH was increased only on the side of the brain ipsilateral to the muscimol injection. Fos expression remained primarily ipsilateral to the injection site in the septohypothalamic, paraventricular hypothalamic (PVN), paratenial thalamic, and lateral habenular nuclei, and medial substantia nigra, but was increased bilaterally in the piriform cortex, supraoptic nucleus, central nucleus of the amygdala, and nucleus of the solitary tract. Smaller numbers of Fos-immunoreactive cells were seen unilaterally in the bed nucleus of the stria terminalis, medial ventral pallidum, arcuate nucleus, and ventral tegmental area and bilaterally in the supraoptic and tuberomammillary nuclei. The labeling in the LH, PVN, and other unilaterally labeled structures provides evidence that these brain regions are components of an AcbSh-mediated neural circuit and suggests that they may be involved in the expression of AcbSh-mediated feeding behavior.