Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia

Edina Szűcs, Szabolcs Dvorácskó, C. Tömböly, Alexandra Büki, G. Kékesi, G. Horváth, S. Benyhe

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Schizophrenia is a serious mental health disorder characterized by several behavioral and biochemicel abnormalities. In a previous study we have shown that mu-opioid (MOP) receptor signaling is impaired in specific brain regions of our three-hit animal model of schizophrenia. Since the cannabinoid system is significantly influenced in schizophrenic patients, in the present work we investigated cannabinoid (CB) receptor binding and G-protein activation in cortical, subcortical and cerebellar regions of control and ‘schizophrenic’ rats. Cannabinoid agonist (WIN-55,212-2 mesylate) mediated G-protein activation was consistently decreased in all areas tested, and the difference was extremely significant in membranes prepared from the cerebellum. Interestingly, the cerebellar activity of WIN-55,212-2 stimulated G-proteins was substantially higher than those of cerebral cortex and subcortical region in control animals, indicating a primordial role of the cannabinoid system in the cerebellum. At the level of radioligand binding, the affinities of the CB receptors were also markedly decreased in the model animals. Capacity of the [3H]WIN-55,212-2 binding was only higher in the cerebellum of ‘schizophrenic’ model rats. Taken together, in all three brain areas of model rats both cannabinoid receptor binding and cannabinoid agonist-mediated G-protein activation were regularly decreased. Our results revealed that besides the opioids, the endocannabinoid – cannabis receptor system also shows impairment in our rat model, increasing its face validity and translational utility.

Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalNeuroscience Letters
Volume633
DOIs
Publication statusPublished - Oct 28 2016

Fingerprint

Cannabinoid Receptors
Cannabinoids
Cannabinoid Receptor Agonists
GTP-Binding Proteins
Schizophrenia
Cerebellum
Brain
Animal Models
Endocannabinoids
Mesylates
mu Opioid Receptor
Cannabis
Reproducibility of Results
Mental Disorders
Cerebral Cortex
Opioid Analgesics
Mental Health
Carrier Proteins
Membranes
Win 55212-2

Keywords

  • Cannabinoid receptors
  • G-protein activation
  • Radioligand binding
  • Schizophrenia animal model
  • WIN-55,212-2 mesylate
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Decreased CB receptor binding and cannabinoid signaling in three brain regions of a rat model of schizophrenia. / Szűcs, Edina; Dvorácskó, Szabolcs; Tömböly, C.; Büki, Alexandra; Kékesi, G.; Horváth, G.; Benyhe, S.

In: Neuroscience Letters, Vol. 633, 28.10.2016, p. 87-93.

Research output: Contribution to journalArticle

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