Electrophysiological characterization of neurons in the prefrontal cortex and hippocampus under pharmacological NMDA receptor blockade
NMDA receptors; Electrophysiology; schizophrenia; prefrontal cortex; hippocampus
Schizophrenia is manifested by symptoms of changes in perception and cognitive functions that are categorized into positive, negative symptoms and cognitive deficits. Despite those being heterogeneous, none of them can be considered pathognomonic. Positive symptoms reflect distinctively altered behavior with psychotic episodes, making the patient unable to distinguish real perceptions from illusions and hallucinations, in addition to causing disordered thoughts and memory. Rather than psychotic episodes, negative symptoms include social withdrawal, apathy, anhedonia, and aphasia. Both types of symptoms are related and affect cognitive systems, such as language, sensory perception and emotional expression (ANDREASEN, 1982; 1995). Some neurotransmitters such as dopamine, glutamate and GABA show physiological abnormality in patients with schizophrenia (FERRARELLI, 2013). The hypothesis that glutamate hypofunction, caused by transmission deficits in its receptors, is strongly related to the symptomatology of the disorder started is analyzed and corroborated from evidence that comes from tests using phencyclidine (PCP), ketamine (QUET) and dizocilpine (MK-801), all N-methyl-D-aspartate glutamate (NMDA) gas receptor antagonists. Due to the discrepancy in the results in rodents and the greater phylogenetic distance between them and humans, the present project aims to compare the electrophysiological records of the prefrontal cortex under the effects of two psychotic drugs (MK-801 and QUET) in the Open Field tests (CA) in nonhuman primates. Eight individuals of Callithrix penicillata allocated in the Biotério do IB of the University of Brasilia were used. For the positioning of the array of electrodes that will make the electrophysiological record, the animals will be submitted to a stereotaxic surgery. After a two-week break after the surgical procedure, the animals were tested in the CA. Habituation sessions were performed and, after a 72- hour interval, there will be 10 sessions of administration of each drug, in pseudo-random order, also with a 72-hour interval between them. Each session lasted 30 minutes. During this period, the spontaneous behavior of the animals (exploratory activity, vigilance and locomotion) and the concomitant neuronal activity through the array of electrodes were recorded. The aim of these sessions was to characterize the spontaneous changes in the activity of neurons in the prefrontal cortex via local field potentials after NMDA receptor blockade. All animals were submitted to both treatments and changes in electrophysiological and behavioral records induced by QUET and MK-801 were compared. The variation of local potentials was correlated with the presentation of spontaneous behaviors.