LACK OF CB1 RECEPTOR ON GABAERGIC NEURONS: EFFECTS IN A PHARMACOLOGICAL MODEL OF SCHIZOPHRENIA

SORIANO DELIA; AGUARELES JOSE; GARCÍA-RINCÓN DANIEL; PARAÍSO-LUNA JUAN; CALTANA LAURA; BRUSCO ALICIA; GALVE-ROPERH ISMAEL

Carlos Paz

Congreso; XXXIV Reunión Anual SAN; 2019

Sociedad Argentina de Investigación en Neurociencias

Schizophrenia is a chronicand progressive mental disorder that combines a variety of clinical symptoms,including psychosis, anhedonia and cognitive deficits. Although the precisemechanisms responsible of schizophrenia development are unknown, several modelsdemonstrate the involvement of dopaminergic, glutamatergic and gabaergicneurotransmission systems. In addition, a cannabinergic hypothesis has been putforward. Endocannabinoid levels and cannabinoid receptor type one (CB1)signalling hence have been implicated in schizophrenia owing to theirneuromodulatory role. The aim of this study was to evaluate the contribution ofCB1 receptor on GABAergic neurons in psychosis like states using the model ofacute systemic administration of the N-Methyl-D-aspartate type ionotropicreceptor (NMDAR) antagonist, MK-801 in wild type (WT) and GABA-CB1-KO mice.Locomotor activity was measured in open field at 30, 60 and 90 minutes afterinjection. Locomotor activity in vehicle-treated GABA-CB1-KO did not differsignificantly from vehicle-treated WT mice, however MK-801 inducedhyperlocomotion persisted longer time in GABA-CB1-KO than WT littermates.This results indicate that CB1 receptors activity onGABAergic neurons protect from the susceptibility to generate a persistentpsychotic-like response. This result, is however in contrast with theattenuation of psychotic responses observed by pharmacological CB1 antagonismor complete deletion of CB1 deletion.