Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam

Int J Neuropsychopharmacol. 2016 Dec 3;19(11):pyw065. doi: 10.1093/ijnp/pyw065. Print 2016 Nov.

Abstract

Background: Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats.

Methods: We used an unbiased stereological method to examine the impact of peripubertal diazepam treatment on parvalbumin interneuron number in the ventral subiculum, dentate gyrus of the hippocampus and the basolateral amygdala.

Results: Methylazoxymethanol acetate rats with peripubertal diazepam showed significantly more parvalbumin interneurons (3355±173 in the ventral subiculum, 1211±76 in the dentate gyrus) than methylazoxymethanol acetate without diazepam (2375±109 and 824±54, respectively). No change was found in the basolateral amygdala.

Conclusions: Peripubertal diazepam attenuated the decrease of parvalbumin in the ventral hippocampus of methylazoxymethanol acetate rats.

Keywords: animal model; diazepam; parvalbumin interneuron; schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antipsychotic Agents / administration & dosage*
  • Behavior, Animal / drug effects*
  • Diazepam / administration & dosage*
  • Disease Models, Animal
  • Down-Regulation
  • Drug Administration Schedule
  • Female
  • Gestational Age
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Interneurons / drug effects*
  • Interneurons / metabolism
  • Methylazoxymethanol Acetate*
  • Parvalbumins / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats, Sprague-Dawley
  • Schizophrenia / chemically induced
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology
  • Schizophrenia / prevention & control*
  • Schizophrenic Psychology*
  • Sexual Maturation

Substances

  • Antipsychotic Agents
  • Parvalbumins
  • Methylazoxymethanol Acetate
  • Diazepam