The Role of Neuropeptide Y in the Nucleus Accumbens

Abstract

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

Keywords: NPY receptors; emotional behavior; fat intake; neuropeptide Y; nucleus accumbens.

Figure 1

(A) Immunohistochemistry of NPY in the NAc of mice. Many medium-sized neurons with fibers are distributed in both the shell and core. Right upper panel shows a region-of-interest at an increased magnification. (B) In situ hybridization histochemistry of NPY mRNA by digoxigenin labeling. Dotted lines depict the medial to ventral border of the NAc and boundary between the core and shell. ac, anterior commissure. LV, lateral ventricle. Scale bars: 100 µm in the main figures and 50 µm in right upper panel.

Figure 2

Schematic of NPY-mediated food intake in the NAc. NPY neurons in the NAc or NPY afferents from hypothalamic arcuate nucleus regulate fat/palatable food intake via accumbal enkephalin neurons expressing Y1 and dopamine D2 receptors. Enk, enkephalin neurons; NPY, neuropeptide Y neurons.

Figure 3

(A) NPY immunohistochemistry in the NAc of NPY-Cre mice at 3 weeks after intraperitoneal injection of diphtheria toxin. The right panel shows NPY immunoreactivity of control mCherry-expressing mice. The left panel shows NPY immunoreactivity in DTR-expressing mice. NPY neurons were ablated after diphtheria toxin exposure in NAc-DTR-expressing mice [129]. ac, anterior commissure. Scale bars: 200 µm. (B) Schematic showing that when accumbal NPY neurons are deleted, mice exhibit increased anxiety, whereas activation of accumbal NPY neurons caused mice to exhibit anxiolytic behavior [129]. DTR, diphtheria toxin receptor; NAc, nucleus accumbens; NPY, neuropeptide Y.