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Canna~Fangled Abstracts

Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB1 receptors: implications for schizophrenia.

By April 18, 2013No Comments

. [Epub ahead of print]

Pub Med

Phencyclidine-induced social withdrawal results from deficient stimulation of cannabinoid CB1 receptors: implications for schizophrenia.

Source

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

Abstract

The neuronal mechanisms underlying social withdrawal, one of the core negative symptoms of schizophrenia, are not well understood. Recent studies suggest an involvement of the endocannabinoid system in the pathophysiology of schizophrenia and, in particular, of negative symptoms. We used biochemical, pharmacological and behavioral approaches to investigate the role played by the endocannabinoid system in social withdrawal induced by sub-chronic administration of phencyclidine (PCP). Pharmacological enhancement of endocannabinoid levels via systemic administration of URB597, an inhibitor of endocannabinoid degradation, reversed social withdrawal in PCP-treated rats via stimulation of CB1 receptors, but reduced social interaction in control animals through activation of a cannabinoid/vanilloid-sensitive receptor. In addition, the potent CB agonist CP55,940 reversed PCP-induced social withdrawal in a CB1-dependent manner, whereas pharmacological blockade of CB1 receptors by either AM251 or SR141716 reduced the time spent in social interaction in control animals. PCP-induced social withdrawal was accompanied by a decrease of anandamide levels in the amygdala and prefrontal cortex, and these deficits were reversed by URB597. As CB1 receptors are predominantly expressed on GABAergic interneurons containing the anxiogenic peptide cholecystokinin (CCK), we also examined whether the PCP-induced social withdrawal resulted from deficient CB1-mediated modulation of CCK transmission. The selective CCK2 antagonist LY225910 blocked both PCP- and AM251-induced social withdrawal, but not URB597 effect in control rats. Taken together, these findings indicate that anandamide-mediated activation of CB1 receptors is crucial for social interaction, and that PCP-induced social withdrawal results from deficient endocannabinoid transmission.Neuropsychopharmacology accepted article preview online, 5 April 2013; doi:10.1038/npp.2013.81.

PMID:

23563893
 
[PubMed – as supplied by publisher] prisoner of the system2
http://www.ncbi.nlm.nih.gov/pubmed/23563893