Intranasal application of secretin, similarly to intracerebroventricular administration, influences the motor behavior of mice probably through specific receptors

J Mol Neurosci. 2012 Nov;48(3):558-64. doi: 10.1007/s12031-012-9839-9. Epub 2012 Jul 1.

Abstract

Secretin and its receptors show wide distribution in the central nervous system. It was demonstrated previously that intravenous (i.v.) and intracerebroventricular (i.c.v.) application of secretin influenced the behavior of rat, mouse, and human. In our previous experiment, we used a special animal model, Japanese waltzing mice (JWM). These animals run around without stopping (the ambulation distance is very limited) and they do not bother with their environment. The i.c.v. secretin attenuated this hyperactive repetitive movement. In the present work, the effect of i.c.v. and intranasal (i.n.) application of secretin was compared. We have also looked for the presence of secretin receptors in the brain structures related to motor functions. Two micrograms of i.c.v. secretin improved the horizontal movement of JWM, enhancing the ambulation distance. It was nearly threefold higher in treated than in control animals. The i.n. application of secretin to the left nostril once or twice a day or once for 3 days more effectively enhanced the ambulation distance than i.c.v. administration. When secretin was given twice a day for 3 days it had no effect. Secretin did not improve the explorative behavior (the rearing), of JWM. With the use of in situ hybridization, we have found very dense secretin receptor labeling in the cerebellum. In the primary motor cortex and in the striatum, only a few labeled cells were seen. It was supposed that secretin exerted its effect through specific receptors, mainly present in the cerebellum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Cerebellum / chemistry
  • Cerebellum / drug effects
  • Corpus Striatum / chemistry
  • Drug Evaluation, Preclinical
  • Exploratory Behavior / drug effects*
  • Female
  • Hyperkinesis / drug therapy
  • Hyperkinesis / genetics
  • In Situ Hybridization
  • Injections, Intraventricular
  • Male
  • Mice
  • Mice, Neurologic Mutants
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Motor Cortex / chemistry
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / analysis
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Gastrointestinal Hormone / agonists
  • Receptors, Gastrointestinal Hormone / analysis
  • Receptors, Gastrointestinal Hormone / physiology
  • Secretin / administration & dosage
  • Secretin / pharmacology*
  • Secretin / therapeutic use

Substances

  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Gastrointestinal Hormone
  • secretin receptor
  • Secretin