INPUT AND OUTPUT OF NEUROPEPTIDE Y IN THE NUCLEUS ACCUMBENS AND PALATABLE FOOD INTAKE

Abstract Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that is widely expressed in the central nervous system and the nucleus accumbens (NAc) is one of the NPY abundant regions as well as arcuate and paraventricular hypothalamic nuclei. NPY in the hypothalamus is well known to enhance food intake. NAc is a hub region of reward and dependence of alcohol and drug intake. We previously suggested that NPY- expressing neurons in the NAc modulate anxiety-behavior using NPY-Cre mice and Cre-dependent AAV. To investigate the projection sites of NAc NPY neurons, we injected AAV(DJ)-FLEX-mCherry into the NAc of NPY-Cre mice. We found mCherry-positive fibers in the lateral hypothalamus (LH), the feeding center. We confirmed this projection to the LH using retrograde tracer. Many NPY nerve fibers are also observed in the NAc. To investigate the origin (s) of NPY fibers in the NAc, we injected AAV(rg)-FLEX- mCherry, permits retrograde access and expression of mCherry to projection neurons, into the NAc in NPY-Cre mice. We found the existence of mCherry-positive cell bodies in the basolateral amygdala (BLA) as well as NAc. Next, we investigated the role of accumbal NPY in the palatable food (high fat diet) intake. We found NPY and NPY Y1 agonist treatment in the NAc induced increase in high fat diet. Then we investigated the involvement of NPY neurons in the BLA projecting to the NAc in high fat diet consumption. Mice stably consume HFD in 1-h during light cycle. To perform projection-specific activation or inactivation of NPY neurons in the BLA, we employed a two-virus strategy, injecting a AAV(rg)-FLEX-Flippase (FLPo) into the NAc and AAV expressing FLPo-dependent hM3Dq-mCherry or - hM4Di-mCherry into the BLA of NPY-Cre mice. CNO-induced activation of BLA NPY neurons projecting to the NAc did not affect to the 1-h HFD intake in the model. On the other hand, CNO-induced inactivation of BLA NPY neurons projecting to the NAc significantly decreased 1-h HFD consumption. These results indicate that NPY neurons in the NAc and those in the BLA that project to the NAc are involved in palatable food consumption in mice.