Activation of ventral pallidum-projecting neurons in the nucleus accumbens via 5-HT 2C receptor stimulation regulates motivation for wheel running in male mice.

Autor: Niitani K; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan., Nishida R; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan., Futami Y; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan., Nishitani N; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan., Deyama S; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan., Kaneda K; Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan. Electronic address: k-kaneda@p.kanazawa-u.ac.jp.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2024 Dec 15; Vol. 261, pp. 110181. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1016/j.neuropharm.2024.110181
Abstrakt: Rodents have a strong motivation for wheel running; however, the neural mechanisms that regulate their motivation remain unknown. We investigated the possible involvement of serotonin (5-HT) systems in regulating motivation for wheel running in male mice. Systemic administration of a 5-HT 1A receptor antagonist (WAY100635) increased the number of wheel rotations, whereas administration of a 5-HT 2A or 5-HT 2C receptor antagonist (volinanserin or SB242084, respectively) decreased it. In the open field test, neither WAY100635 nor volinanserin affected locomotor activity, whereas SB242084 increased locomotor activity. To identify the brain regions on which these antagonists act, we locally injected these into the motivational circuitry, including the nucleus accumbens (NAc), dorsomedial striatum (DM-Str), and medial prefrontal cortex (mPFC). Injection of SB242084 into the NAc, but not the DM-Str or mPFC, reduced the number of wheel rotations without altering locomotor activity. The local administration of WAY100635 or volinanserin to these brain regions did not affect the number of wheel rotations. Immunohistochemical analyses revealed that wheel running increased the number of c-Fos-positive cells in the NAc medial shell (NAc-MS), which was reduced by systemic SB242084 administration. In vitro slice whole-cell recordings showed that bath application of the 5-HT 2C receptor agonist lorcaserin increased the frequency of spontaneous excitatory and inhibitory postsynaptic currents in the ventral tegmental area (VTA)-projecting neurons, whereas it only increased the frequency of spontaneous excitatory postsynaptic currents in ventral pallidum (VP)-projecting neurons in the NAc-MS. These findings suggest that the activation of VP-projecting NAc-MS neurons via 5-HT 2C receptor stimulation regulates motivation for wheel running.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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