Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice

Brain Res. 2007 Feb 2;1131(1):173-80. doi: 10.1016/j.brainres.2006.11.007. Epub 2006 Dec 14.

Abstract

Reelin is an extracellular matrix protein, secreted by GABAergic interneurons, that provides a signal for neural plasticity. A downregulation of reelin may be a factor to be considered in the study of major psychiatric disorders. The heterozygous reeler mouse model, thus, may be important to reveal those alterations in behavioral phenotype produced by reduced neural plasticity. Heterozygous (HZ) and wild-type (WT) mice were tested for anxiety-related behavior, motor impulsivity, and morphine-induced analgesia. Heterozygous mice showed significantly lower levels of anxiety- and risk-assessment-related behaviors in the elevated plus-maze during adolescence, in the absence of basal changes in general locomotion. Adult mice were assessed for profiles of impulsive behavior in operant chambers, and HZ mice exhibited elevated levels of motor impulsivity. When mice were assessed in nociception tests, a genotype difference in morphine-induced analgesia was found, and these results were confirmed by measurement of mu-receptors in the midbrain. The basal behavioral profile of the HZ genotype reveals important differences, consistent with decreased behavioral inhibition and emotionality, which can be revealed as early as in adolescence, together with slight increment of impulsive behavior and altered pain threshold and at the adult age. The HZ genotype can thus represent a useful animal model for the study of behavioral disorders consequent to reduced neural plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Anxiety Disorders / genetics*
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Brain Chemistry / genetics*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Disease Models, Animal
  • Drug Resistance / drug effects
  • Drug Resistance / genetics
  • Drug Tolerance / genetics
  • Emotions / physiology
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Heterozygote
  • Impulsive Behavior / genetics*
  • Impulsive Behavior / metabolism
  • Impulsive Behavior / physiopathology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Mice
  • Mice, Neurologic Mutants
  • Morphine / pharmacology
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Nerve Tissue Proteins / genetics*
  • Neuronal Plasticity / genetics
  • Pain / drug therapy
  • Pain / genetics*
  • Pain / metabolism
  • Pain Threshold / drug effects
  • Pain Threshold / physiology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / metabolism
  • Reelin Protein
  • Serine Endopeptidases / genetics*

Substances

  • Analgesics, Opioid
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, Opioid, mu
  • Reelin Protein
  • Morphine
  • Reln protein, mouse
  • Serine Endopeptidases