Long-lasting, distinct changes in central opioid receptor and urinary bladder functions in models of schizophrenia in rats

Orsolya Kekesi, Gabor Tuboly, M. Szücs, Erika Birkas, Zita Morvay, G. Benedek, G. Horváth

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Ketamine treatments and social isolation of rats reflect certain features of schizophrenia, among them altered pain sensitivity. To study the underlying mechanisms of these phenomena, rats were either housed individually or grouped for 33 days after weaning, and treated with either ketamine or saline for 14 days. After one month re-socialization, the urinary bladder capacity by ultrasound examination in the anesthetized animals, and changes of μ-opioid receptors by saturation binding experiments using a specific μ-opioid agonist [3H]DAMGO were determined. G-protein signaling was investigated in DAMGO-stimulated [35S]GTPγS functional assays. Ketamine treatment significantly decreased the bladder volume and isolation decreased the receptor density in cortical membranes. Among all groups, the only change in binding affinity was an increase induced by social isolation in the cortex. G-protein signaling was significantly decreased by either ketamine or social isolation in this tissue. Ketamine treatment, but not housing, significantly increased μ-opioid receptor densities in hippocampal membranes. Both ketamine and isolation increased the efficacy, while the potency of signaling was decreased by any treatment. Ketamine increased the receptor density and G-protein activation; while isolation decreased the efficacy of G-protein signaling in hippocampal membranes. The changes in the co-treated group were similar to those of the isolated animals in most tests. The distinct changes of opioid receptor functioning in different areas of the CNS may, at least partially, explain the augmented nociceptive threshold and morphine potency observed in these animals. Changes in the relative urinary bladder suggest a detrusor hyperreflexia, another sign of schizophrenia.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalEuropean Journal of Pharmacology
Volume661
Issue number1-3
DOIs
Publication statusPublished - Jul 1 2011

Fingerprint

Ketamine
Opioid Receptors
Schizophrenia
Urinary Bladder
GTP-Binding Proteins
Social Isolation
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Membranes
Abnormal Reflexes
Socialization
Therapeutics
Weaning
Morphine
Opioid Analgesics
Pain

Keywords

  • Opioid
  • Receptor binding
  • Schizophrenia
  • Social isolation
  • Urinary bladder

ASJC Scopus subject areas

  • Pharmacology

Cite this

Long-lasting, distinct changes in central opioid receptor and urinary bladder functions in models of schizophrenia in rats. / Kekesi, Orsolya; Tuboly, Gabor; Szücs, M.; Birkas, Erika; Morvay, Zita; Benedek, G.; Horváth, G.

In: European Journal of Pharmacology, Vol. 661, No. 1-3, 01.07.2011, p. 35-41.

Research output: Contribution to journalArticle

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