2,5-Anhydro-D-mannitol induces Fos-like immunoreactivity in hindbrain and forebrain: relationship to eating behavior

Injection of the fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), stimulates eating behavior in rats. Previous studies have shown that administration of 2,5-AM in doses that elicit eating induces Fos-like immunoreactivity (Fos-li) primarily in hindbrain structures, including the nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (PBN). To more closely assess the relationship between neural activation and the eating response to 2,5-AM treatment, we measured food intake and brain Fos-li in rats given a range of doses of 2,5-AM. The numbers of neurons showing Fos-li were quantified by computerized image analysis. Doses of 2,5-AM that reliably stimulated food intake induced Fos-li in both the hindbrain and forebrain, including in the NTS, AP, lateral PBN, central lateral nucleus of the amygdala, dorsal lateral bed nucleus of the stria terminalis (BNSTdl), anterior paraventricular nucleus of the thalamus, supraoptic nucleus, subfornical organ, and paraventricular hypothalamic nuclei. A low dose of 2,5-AM that did not elicit eating increased Fos-li marginally only in the AP, PBN, and BNSTdl. The results suggest that 2,5-AM treatment activates a vagal afferent pathway projecting from the hindbrain to forebrain that is involved in initiating the eating response to the fructose analogue.