EFECTOS AGUDOS Y CRÓNICOS DE LA CORTICOSTERONA SOBRE LA INMOVILIDAD DE LA RATA Y LA PRODUCCIÓN DE RADICALES LIBRES EN CEREBRO, HÍGADO Y MÚSCULO

Abstract

The immobility response (IR) is also known as "tonic immobility," "behavioural arrest," "animal hypnosis", etc is considered an innate antipredatory behavior characterized by the absence of movement, greater or lesser degree of muscular activity and lack of response in relation to external stimuli. Experimentally, the IR is commonly produced manually forcing an animal in an supine position and held that position until the animal is immobilized. Part of the mechanism (s) neural (s) IR involves the bulbo-pontine reticular formation, with influences from other parts of the brain, particularly the limbic system. It has been observed that the IR is longer in stressed animals, and systemic injection of corticosterone (CORT) also promotes this behavior. At present, the anatomical regions of the brain involved in the modulation of IR are unknown. Therefore, the present study was undertaken to determine if some pontine areas could be targeted for the modulation of the IR. Because CORT has affinity to mineralocorticoid and glucocorticoid receptors (MR) (GR) and because the expression of these receptors have been shown to be modified by chronic high CORT levels. It was the purpose, too, of this work to assess some of the behavioral disorders associated with HPA axis dysregulation (anxiety, depression, locomotor activity) and alterations associated with the effect of CORT (weight, free radical formation.) It used male Wistar rats 250-300 g, which were kept in standard animal care conditions. Stereotactic surgery was performed and cannulas were placed on the oral pontine nucleus (PnO). Medial lemniscus (mla) and paramedian raphe (PMR) and injected 1μL corticosterone 21-acetate (CORT) 0.05 mg / 1.0 mL. Spironolactone (SPIRO) (0.5 μg/1.0 mL) and mifepristone (MIFEP) (0.5 μg/1.0 mL) were dissolved in vehicle (VEH: 45% hydroxypropyl-β-cyclodextrin 0.1 in phosphate buffer at pH 7.4). The drugs were administered via a silastic tube connected to a Hamilton syringe of 1 μL. After administration was measured at 3, 7, 15, 30, 60 and 120 minutes the response duration of immobility and locomotor behavior using the Videomex-V. Another group of rats were given 1 ml / kg ip CORT (5 mg / kg ip.) or VEH for 12 days. At the end of treatment was measured IR, locomotor activity, body and organ weight, food intake, water consumption, blood glucose, enzymatic activity of samples of blood superoxide dismutase (SOD), total antioxidant blood samples (TAS), formation of thiobarbituric acid reactive species (TBARS) of blood, muscle and liver free radical formation (RL), by the method of electron paramagnetic resonance (EPR), in addition to plus maze test and forced swimming test. The unilateral microinjection into the nucleus pontis oralis (PnO) of 1.0 μL of CORT (0.05 μg/1.0 mL) in rats resulted in clear behavioral responses. Animals show an increase in the duration of the IR-induced by calmping the neck (in this type of induction, there is also turning and restricted body), and there was also an increase in locomotor activity in the open field, which was prevented by treatments in PnO with 1.0 mL of spironolactone, an antagonist of mineralocorticoid receptors (0.5 mg / mL) or 1.0 mL of mifepristone glucocorticoid receptor antagonist (0.5 mg / mL). By contrast, these behavioral responses were not observed when the CORT (0.05 μg / 1.0 mL) was microinjected into the medial lemniscus area (mla) or the paramedian raphe (PMR). Moreover, a significant decrease on day 12 in body weight and weight of the adrenal glands. There were no significant differences in blood glucose, also in TBARS of muscle, liver and brain. SOD levels increased significantly in CORT respect VEH rats and TAS was lower in CORT compared to VEH. Measurement of FR by EPR shows significant difference in brain in CORT rats administered with respect to VEH. The performance tests indicated a decrease in locomotor activity after repeated administration of CORT, in the plus maze test and forced swimming test was evident, respectively, a reduction of time in open arms and an increased rest time, during test forced swimming, decreased swimming time. Our data support the idea that under stress, glucocorticoids released from the adrenal glands to produce PnO arrive at a state of hyper arousal, which in turn extends the life of IR. Continuous stimulation whit CORT provoque a dysfunction of the hypothalamic-pituitary-adrenal axes and availability of MR and GR receptors by a possible reduction to low, which decays IR and locomotor activity. Our data support the possibility that alterations in the HPA is one of the causes of increased anxiety and depression,