Peripheral injected cholecystokinin-8S modulates the concentration of serotonin in nerve fibers of the rat brainstem

Peptides. 2014 Sep:59:25-33. doi: 10.1016/j.peptides.2014.07.003. Epub 2014 Jul 10.

Abstract

Serotonin and cholecystokinin (CCK) play a role in the short-term inhibition of food intake. It is known that peripheral injection of CCK increases c-Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract (NTS) in rats, and injection of the serotonin antagonist ondansetron decreases the number of c-Fos-IR cells in the NTS. This supports the idea of serotonin contributing to the effects of CCK. The aim of the present study was to elucidate whether peripherally injected CCK-8S modulates the concentration of serotonin in brain feeding-regulatory nuclei. Ad libitum fed male Sprague-Dawley rats received 5.2 and 8.7 nmol/kg CCK-8S (n=3/group) or 0.15M NaCl (n=3-5/group) injected intraperitoneally (ip). The number of c-Fos-IR neurons, and the fluorescence intensity of serotonin in nerve fibers were assessed in the paraventricular nucleus (PVN), arcuate nucleus (ARC), NTS and dorsal motor nucleus of the vagus (DMV). CCK-8S increased the number of c-Fos-ir neurons in the NTS (mean±SEM: 72±4, and 112±5 neurons/section, respectively) compared to vehicle-treated rats (7±2 neurons/section, P<0.05), but did not modulate c-Fos expression in the DMV or ARC. Additionally, CCK-8S dose-dependently increased the number of c-Fos-positive neurons in the PVN (218±15 and 128±14, respectively vs. 19±5, P<0.05). In the NTS and DMV we observed a decrease of serotonin-immunoreactivity 90 min after injection of CCK-8S (46±2 and 49±8 pixel/section, respectively) compared to vehicle (81±8 pixel/section, P<0.05). No changes of serotonin-immunoreactivity were observed in the PVN and ARC. Our results suggest that serotonin is involved in the mediation of CCK-8's effects in the brainstem.

Keywords: C-Fos; Cholecystokinin; Dorsal motor nucleus of the vagus; Nucleus of the solitary tract; Paraventricular nucleus of the hypothalamus; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Stem / drug effects*
  • Brain Stem / metabolism*
  • Cholecystokinin / administration & dosage*
  • Cholecystokinin / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • Nerve Fibers / drug effects*
  • Nerve Fibers / metabolism*
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*

Substances

  • Peptide Fragments
  • cholecystokinin 8
  • Serotonin
  • Cholecystokinin