Banca de DEFESA: SONIA CAROLINA GUERRERO PRIETO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : SONIA CAROLINA GUERRERO PRIETO
DATA : 12/11/2020
HORA: 14:00
LOCAL: Remoto UFABC Campus SBC
TÍTULO:

EXTRAPYRAMIDAL SIDE EFFECTS INDUCED BY PSYCHOTROPIC, METOCLOPRAMIDE AND L-NOARG DRUGS WITH DIFFERENTIAL STRIATAL FOS FAMILY PROTEIN EXPRESSION AND NADPH-DIAPHORASE ACTIVITY IN DORSAL AND LATERAL STRIATUM

PÁGINAS: 142
GRANDE ÁREA: Ciências da Saúde
ÁREA: Medicina
SUBÁREA: Psiquiatria
RESUMO:

Previous research indicates that acute, subchronic and chronic administration of typical antipsychotics like haloperidol (Hal) and atypicals like clozapine (Clz) and olanzapine (Olz), an antiemetic like metoclopramide (MCP) can induce extrapyramidal side effects (EPS). (i) Our objective was to evaluate the motor side effects after the acute administration of Hal, MCP or L-NOARG, a NO inhibitor, and to correlate their behavior modulation with c-Fos, nNOS and NADPH-diaphorase (NADPH-d) in the striatum of male Swiss mice that received Hal 0.1-1 mg / kg; MCP 1-45 mg / kg .; L-NOARG 15 - 45 mg / kg .; or saline (i.p). Catalepsy and changes in motor activity appeared after administration of D2R blockers, with increased expression of c-Fos in the dorsal striatum, in addition to an increase in NADPH-d activity. In contrast, the higher catalytic doses of L-NOARG caused a reduction in the expression of c-Fos in the DL and NAc striatum, but also resulted in increased NADPH-d activity in the dorsal striatum. Previously, in several studies it was found that the co-administration of L-NOARG produces tolerance to the development of motor alterations by Hal and by L-NOARG itself. Then, (ii) our interest was to study whether NO inhibition modulates catalepsy induced by subchronic treatment with atypical antipsychotics such as Olz 15 mg / kg and Clz 20 mg / kg, in male C57Bl / 6J mice. Subchronic administration of all antipsychotics produced catalepsy, but cross-tolerance was observed only between L-NOARG 15, and Clz 20,. This cross-tolerance effect was accompanied by decreased expression of the FosB protein in the dorsal striatum and in the core region of the nucleus accumbens, and reduced NADPH-d activity in the lateral and ventral dorsum striatum. Subsequently, (iii) we studied EPS induced by subchronic administration (5 days) of therapeutic doses of MCP 1, 5 and 8 mg / kg / ip, in male Swiss mice, with intermittent coadministration of L-NOARG 15 and 30 mg / kg + MCP 8 mg / kg or Hal 0.5 mg / kg / ip. A significant cross-tolerance was observed on the last day for the groups L-NOARG 15 + MCP 8 and L-NOARG 15 + Hal 0.5, confirming our first study, where L-NOARG did not impair motor activity, with the same dose. Interestingly, L-NOARG itself does not appear to change performance on rotarod. Finally, after verifying that therapeutic doses of MCP induce EPS, we examine whether EPS suffers tolerance after chronic administration (21 days) of MCP 5 or 8 mg / kg / ip, with the correlation of FosB, nNOS, NADPH-d and Darpp32 -Expression of Thr75 in the striatum, using male Swiss mice. Catalepsy, tardive dyskinesia (TD) and motor activity were evaluated once a week. A significant catalytic effect and an increase in the number of CMV was observed every week for MCP 8 mg / kg, accompanied by an increase in the expression of FosB in the DL and DM regions, but a significant decrease in the expression of Darpp32-Thr75 in the DL region. In general, motor alteration may appear after acute, subchronic and chronic administration of D2R blockers, without tolerance, with therapeutic doses in preclinical trials.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1872537 - MARCELA BERMUDEZ ECHEVERRY
Membro Titular - Examinador(a) Interno ao Programa - 1675707 - FULVIO RIELI MENDES
Membro Titular - Examinador(a) Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Titular - Examinador(a) Externo à Instituição - MARIZA BORTOLANZA
Membro Titular - Examinador(a) Externo à Instituição - ANA CAROLINA ISSY - USP
Membro Suplente - Examinador(a) Interno ao Programa - 1771857 - CARLOS ALBERTO DA SILVA
Membro Suplente - Examinador(a) Interno ao Programa - 1669152 - DANIEL CARNEIRO CARRETTIERO
Membro Suplente - Examinador(a) Externo à Instituição - CECILIA CAFE - USP
Membro Suplente - Examinador(a) Externo à Instituição - NÚBIA MANTOVAN FARDIN - UNIP