Impairments of social behavior and memory after neonatal gastrin-releasing peptide receptor blockade in rats: Implications for an animal model of neurodevelopmental disorders

Neuropharmacology. 2007 Mar;52(3):724-32. doi: 10.1016/j.neuropharm.2006.09.020. Epub 2006 Nov 13.

Abstract

The gastrin-releasing peptide receptor (GRPR) has been implicated in central nervous system (CNS) diseases, including neurodevelopmental disorders associated with autism. In the present study we examined the effects of GRPR blockade during the neonatal period on behavioral measures relevant to animal models of neurodevelopmental disorders. Male Wistar rats were given an intraperitoneal (i.p.) injection of either saline (SAL) or the GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095; 1 or 10mg/kg) twice daily for 10days from postnatal days (PN) 1 to 10. Animals treated with RC-3095 showed pronounced deficits in social interaction when tested at PN 30-35 and impaired 24-h retention of memory for both novel object recognition (NOR) and inhibitory avoidance (IA) tasks tested at PN 60-71. Neither short-term memory tested 1.5h posttraining nor open field behavior were affected by neonatal GRPR blockade. The implications of the findings for animal models of neurodevelopmental disorders are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Avoidance Learning / drug effects
  • Body Weight / drug effects
  • Bombesin / analogs & derivatives*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects
  • Female
  • Inhibition, Psychological
  • Injections, Intraperitoneal / methods
  • Locomotion / drug effects
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / physiopathology
  • Motor Activity / drug effects
  • Peptide Fragments*
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Receptors, Bombesin / antagonists & inhibitors*
  • Receptors, Bombesin / physiology*
  • Social Behavior Disorders / chemically induced*
  • Social Behavior Disorders / physiopathology

Substances

  • Peptide Fragments
  • Receptors, Bombesin
  • bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-
  • Bombesin