Anales RANF

P.41 THE EFFECT OF P2X7 RECEPTOR DEFICIENCY ON C-FOS ACTIVATION IN AN ACUTE PCP INDUCED SCHIZOPHRENIA MODEL IN MICE Stefano Calovi 1, 2 and Beáta Sperlágh 1 1 Laboratory of Molecular Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. 2 János Szentágothai School of Neurosciences, Semmelweis University School of PhD Studies, Budapest, Hungary. P2X7 receptor (P2X7R) is an ATP-gated ionotropic channel expressed in the central nervous system by different cell populations. Genetic ablation or pharmacological antagonism of P2X7R shows protective effect in a wide range of models for psychiatric disorders. Our group recently described (Koványi et al. 2016) that in a low-dose (2-5 mg/kg) phencyclidine (PCP) induced model of schizophrenia, the blockade or deletion of the p2rx7 gene attenuates PCP-induced hyperlocomotion, stereotype behavior and social withdrawal in mice. Moreover, it attenuates PCP-induced changes in the transcriptional regulation of proteins, affecting excitatory and inhibitory transmission and synaptic function in the prefrontal cortex. A high dose of PCP delivered systemically, affects the activity and connectivity of different brain areas, mimicking the pattern of activation during schizophrenic episodes in humans (Parsonen et al. 2017). The medial prefrontal cortex (mPFC) in mice, corresponding to the dorsolateral cortex in humans, is of particular interest for what concerns schizophrenia-related cognitive deficits. In this study, we have studied the effect of PCP in in the mPFC using a sub-chronic (10 mg/kg ip per 7 days, + 3-10 days of washout) and an acute (10 mg/kg ip) model. In case of sub-chronic PCP model, we could not observe any notable signs of inflammatory reaction either in WT or P2X7R KO animals. After a single injection of PCP (10 mg/kg ip), P2X7R KO mice displayed a lower number of c-fos immunoreactive neurons in the mPFC. The behavior of the treated P2X7 receptor KO animals was also different, displaying lower PCP-induced hyperlocomotion and stereotypic activity. Exploring how the genetic ablation of p2rx7 gene plays a role in counteracting the acute psychotomimetic effect of PCP could reveal novel function of the protein as well as help to disentangle the neurological substrate of the action of the arylcycloexyl anesthetic drugs.