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.

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“…This mirrors studies that show that parvalbumin (PV) interneuron and SOM innervation is required for the survival of new abGCs (193,194). The NPY receptor is Gi/o coupled, and while the pathway that regulates neurogenesis is thought to proceed through the Y1 receptor subtype, there are also receptor subtypes 2-6 -however, 6 is rodent specific and a pseudogene in humans (195,196). A subtype of NPY interneuron called the neurogliaform cell contains en passant boutons that release GABA into the extracellular space which largely act on extrasynaptic GABAB receptors to maintain basal inhibition in the brain (18,197,198).…”

Hedonic eating, obesity, and addiction result from increased neuropeptide Y in the nucleus accumbens during human brain evolution

“…Van den Heuvel et al ( 20 ) found that NPY injections into the NAc of rats induce a specific preference for fat, but not sugar or standard chow in these rodents, an effect that is thought to be mediated by Y1 receptors on enkephalinergic neurons (reviewed in ref. 48 ). Pandit et al ( 49 ) measured the effects of NPY infusion into the lateral hypothalamus, NAc, and ventral tegmental area on the motivation for, and consumption of, sucrose.…”

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“… 122 NPY is widely distributed in the nervous system and is particularly highly expressed in NAc and BLA. 170 Numerous studies have demonstrated that NPY levels are negatively correlated with anxiety, 171 which may be related to neuroprotective effects by promoting neurogenesis and neuroplasticity, 172 and decreasing amygdala excitability. 173 NPY has been reported to be involved in the neuroplastic protective effects of AEA, and inhibition of its expression antagonizes the effects of URB597 in suppressing PTSD behavior.…”