G-protein coupled receptors that signal bitter taste (T2Rs) are expressed in the mucosal lining of the oral cavity and gastrointestinal (GI) tract. In mice, intragastric (i.g.) infusion of T2R ligands activates Fos expression within the caudal viscerosensory portion of the nucleus of the solitary tract (NTS) through a vagal pathway (10). The present study was performed in rats to further characterize the distribution and chemical phenotypes of brainstem and forebrain neurons activated to express Fos after i.g. gavage of T2R ligands, and to determine a potential behavioral correlate of this central neural activation. Compared to relatively low brainstem and forebrain Fos expression in control rats gavaged i.g. with water, rats gavaged i.g. with T2R ligands displayed significantly increased activation of neurons within the caudal medial (visceral) NTS and caudal ventrolateral medulla, including noradrenergic neurons, and within the lateral parabrachial nucleus, central nucleus of the amygdala, and paraventricular nucleus of the hypothalamus. A behavioral correlate of this Fos activation was evidenced when rats avoided consuming flavors that previously were paired with i.g. gavage of T2R ligands. While unconditioned aversive responses to bitter tastants in the oral cavity are often sufficient to inhibit further consumption, a second line of defense may be provided post-ingestively by ligand-induced signaling at GI T2Rs that signal the brain via vagal sensory inputs to the caudal medulla.