Efeitos da hipóxia-isquemia perinatal sobre o comportamento motor, distribuição da Tirosina Hidroxilase na substância negra e da NADPH diaforase no hipocampo durante o desenvolvimento em ratos / Effects of hypoxia-ischemia under motor behavior, tyrosine hydroxylase distribution in the nigra substantia and the diaphorase NADPH in hippocampus in rats

A hipóxia isquemia (HI) pré-natal é uma das principais causas de mortalidade e doenças neurológicas crônicas em neonatos, que podem apresentar déficits remanentes como: retardamento, paralisia cerebral, dificuldade de aprendizado ou epilepsia. Estes prejuízos, provavelmente, estão relacionados com o atraso no desenvolvimento neural, astrogliose e com a perda de neurônios e oligodendrócitos. Déficits funcionais e cognitivos estão associados à degeneração de vias dopaminérgicas e de estruturas hipocampais. A enzima tirosina hidroxilase (TH) é a enzima limitante na síntese de dopamina e seus níveis são alterados em eventos de HI. O óxido nítrico (NO) é um gás difusível que atua modulando diferentes sistemas, participando de eventos como plasticidade sináptica e neuromodulação no sistema nervoso central e é produzido em grandes quantidades em eventos de injúria e inflamação, como é o caso da HI. O presente estudo teve por objetivos avaliar, utilizando o modelo criado por Robinson e colaboradores em 2005, os efeitos da HI sobre o comportamento motor e avaliar o desenvolvimento de estruturas encefálicas relacionadas a este comportamento como a substância negra (SN) e o complexo hipocampal. A HI foi induzida a partir do clampeamento das artérias uterinas da rata grávida, por 45 minutos no décimo oitavo dia de gestação (grupo HI). Em um grupo de fêmeas a cirurgia foi realizada, mas não houve clampeamento das artérias (grupo SHAM). A avaliação do comportamento motor foi realizada com os testes ROTAROD e de campo aberto em animais de 45 dias. Os encéfalos foram processados histologicamente nas idades de P9, P16, P23 e P90, sendo então realizada imunohistoquímica para TH e histoquímica para NADPH diaforase (NADPH-d), para avaliação do NO. Nossos resultados demonstraram redução da imunorreatividade para a TH em corpos celulares na SN aos 16 dias no grupo HI e aumento na imunorreatividade das fibras na parte reticulada aos 23 dias, com a presença de corpos celulares...

Perinatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can show permanent effects such as mental retardation, cerebral palsy, learning difficulty and epilepsy. It is probable that these impairs may be related to a delay in the neural development, astrogliosis and to the death of neurons and oligodendrocytes. Cognitive and functional deficits are related to degeneration of dopaminergic pathways and hippocampus. The enzyme tyrosine hydroxylase (TH) is a limiting step in the dopamine synthesis and its levels are impaired in HI insults. Nitric oxide (NO) is a diffusible gas that acts by modulating different systems and participates in several phenomena such as synaptic plasticity and neuromodulation in the central nervous system and is produced in higher levels in events of injury and inflamation as in the case of HI. This study aimed to evaluate the effects of HI on the motor behavior and to evaluate the development of brain structures related to this behavior as the substantia nigra (SN) and the hippocampal complex, using the model developed by Robinson and colleagues in 2005. HI was induced by clamping the uterine arteries of pregnant rats, for 45 minutes, on the eighteenth day of gestation (group HI). In a group of females, the surgery was performed, but no clamping of the arteries (group SHAM) was made. Assessment of motor behavior was performed with the ROTAROD test and open field test in animals of 45 days (P45) of age. The brains were processed histologically at ages P9, P16, P23 and P90, and then submitted to immunohistochemistry for TH and NADPH diaphorase (NADPH-d) histochemistry for evaluation of NOS. Our results demonstrated an apparent decrease in TH immunoreactivity in cell bodies in the SN at P16 in the HI group and an increase in immunoreactivity of the fibers in the SN pars reticulata at P23 with the presence of TH immunoreactive cell bodies at this same region in the HI group...

Chronic amantadine treatment enhances the sexual behaviour of male rats.

The acute administration of amantadine (AMA), a dopaminomimetic and NMDA glutamatergic receptor antagonist also used as an anti-Parkinsonian agent, stimulates male rat sexual behaviour. However it remains unclear whether long term AMA supplementation might also provoke a similar increase in male rat sexual conduct. In the present study, male rats were administered AMA (5-50 mg/kg/day) or vehicle daily for 21 days and their sexual response was monitored weekly. Chronic treatment with AMA effectively increased the sexual response of male rats, similarly to what had been observed before with acute amantadine treatment. The main effect of chronic AMA treatment occurs in arousal and in ejaculatory response, whilst the excitatory component was not affected. The 21-day treatment with AMA did not lead to tolerance, suggesting that perhaps AMA could be used in male human patients to prevent sexual inhibition caused by anti-depressant and anti-psychotic agents.

Preventing L-NAME inhibitory effects on rat sexual behavior with hydralazine, isradipine or captopril co-treatment.

The effects of the chronic oral treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), separately or in combination with isradipine, captopril or hydralazine, on standard and temporal patterning sexual behavior of male rats were evaluated. L-Arginine and filtered water were used as control. L-NAME treatment decreased the copulatory rate and hit rate factors of sexual behavior. However, the initiation factor and temporal patterning were less modified by the drug. After 14 days of L-NAME treatment suspension the male rat sexual response was recovered. The three antihypertensive agents were able to reverse partially or totally the inhibitory effects of L-NAME, suggesting that the chronic oral treatment with L-NAME induces penile erection dysfunction by peripheral mechanisms. The present results suggest that chronic oral treatment with nitric oxide (NO) synthase inhibitor can be a relevant and powerful peripheral erectile dysfunction model to evaluate the effects of drugs on erectile function of male rats.