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| Author(s): |
Cleiton Lopes Aguiar
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2014-05-20 |
| Examining board members: |
João Pereira Leite;
Norberto Garcia Cairasco;
Jaime Eduardo Cecilio Hallak;
Marcio Flavio Dutra Moraes;
Claudio Marcos Teixeira de Queiroz
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| Advisor: | João Pereira Leite; Rodrigo Neves Romcy Pereira |
| Abstract | |
Psychotic disorders affect around 20% of the patients with temporal lobe epilepsy (TLE). This condition is resulted of dysfunctions in different levels of neurobiological organization. ln animal models, it has been shown that the excitatory/inhibitory unbalance in cortico-limbic circuits produces secondary dysfunctions in the dopaminergic system, leading to psychotic-like behavioral abnormalities. At long-term, the synaptic plasticity dysfunction in the cortex seems to underlie the negative symptoms and cognitive deficits observed in schizophrenia or psychosis associated to TLE. The present work aimed to characterize the effects of hippocampal after-discharge (AD; putative model of post-ictal psychosis) or ketamine S+ (KET-S+; pharmacological model of psychosis) on the synaptic plasticity and oscillatory patterns in the CA1-medial prefrontal cortex (mPFC) pathway. Also, we tested whether the induction of cortical long-term potentiation (LTP) was able to prevent the presynaptic plasticity impairment induced by AD or KET-S+. Electrodes were stereotaxically positioned into CA1 and mPFC in urethane-anesthetized rats. Squared-monophasic paired-pulses of electrical stimuli were applied to CA1 in order to evoke field post-synaptic potentials (fPSP1 and fPSP2) in the mPFC every at 0,05 hz. Short-term plasticity was evaluated by measuring paired-pulse facilitation (PPF), defined as the amplitude ratio fpSP2/fpSP1. After 90min of baseline recordings, three independent groups of animals received hippocampal-AD, KET-S+ (12.5mg/kg, i.p.) or vehicle (NaCI 0.15M) followed by 120min of evoked response monitoring. ln an additional experiment, two applications of high-frequency stimuli (HFS) were performed at 30 and 60min after baseline. Thirty minutes after the second HFS, the rats received KET-S+, AD or vehicle and their cortical evoked potentials were monitored for further 120min. Our results showed that AD significantly decreased (- 50%; p<0,05 - Two way ANOVA repeated measures) whereas KET-S+ enhanced (+10%) CA1-mPFC basal synaptic transmission. ln addition, AD and KET-S+ similarly impaired short-term plasticity in the mPFC (-15%). lnterestingly, induction of LTP in the mPFC prevented the PPF disruption and the aberrant enhancement of the cortical comodulation (high-gamma amplitude/delta phase) induced by KET and AD. Altogether, our findings support recent evidences that positive allosteric modulators of NMDA and AMPA receptors attenuate cognitive impairments in animal models of psychosis. Therefore, HFS in CA1 might be a useful tool to better understand how to prevent synaptic plasticity disruptions observed in experimental models of psychosis and post-ictal psychosis. (AU) | |