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

• Published in: European journal of pharmacology Vol. 661; no. 1; pp. 35 - 41
• Main Authors: Kekesi, Orsolya, Tuboly, Gabor, Szucs, Maria, Birkas, Erika, Morvay, Zita, Benedek, Gyorgy, Horvath, Gyongyi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-07-2011; Elsevier
• Subjects: Adult and adolescent clinical studies; Animals; Biological and medical sciences; Central Nervous System - metabolism; Central Nervous System - pathology; Central Nervous System - physiopathology; Disease Models, Animal; GTP-Binding Proteins - metabolism; Male; Medical sciences; Opioid; Organ Size; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Wistar; Receptor binding; Receptors, Opioid - metabolism; Receptors, Opioid, mu - metabolism; Schizophrenia; Schizophrenia - metabolism; Schizophrenia - pathology; Schizophrenia - physiopathology; Signal Transduction; Social isolation; Time Factors; Urinary bladder; Urinary Bladder - metabolism; Urinary Bladder - pathology; Urinary Bladder - physiopathology; Opioid; Schizophrenia; Urinary bladder; Receptor binding; Social isolation; Rat; Opioid receptor; Rodentia; Opiates; Opioid peptide; Psychosis; Vertebrata; Mammalia; Urinary system; Animal; Models; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.04.022

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.