Hypothyroidism during neonatal and perinatal period induced by thyroidectomy of the mother causes depressive-like behavior in prepubertal rats.

The objective of this study was to see if neonatal and perinatal hypothyroidism caused anxiety and depressive-like behaviors. Twenty female Wistar rats were randomly divided into two groups: 1) thyroidectomy caused hypothyroidism, in which the thyroid gland had been removed and the parathyroid reimplanted; and 2) false thyroidectomy. The thyroidectomy was made on rats anesthetized with ketamine-xylazine. The rats were mated and one day after giving birth, eight pups were assigned to each group randomly and they were distributed into two groups: a hypothyroid group containing male pups of a hypothyroid mother with a hypothyroid wet nurse; and a euthyroid group of male pups of a euthyroid mother with a euthyroid wet nurse. We analyzed the behavioral test at a prepubertal age. The neonatal and perinatal hypothyroidism caused by the mother's thyroidectomy caused a decrease in body weight and length. We found that the neonatal and perinatal hypothyroidism enhanced the total exploratory activity without affecting social contact and the time spent in the open and closed arms in an elevated plus-maze. The hypothyroidism caused immobility without altering the lower climbing duration in the swimming test. This study shows a novel model to cause neonatal and perinatal hypothyroidism without using pharmacological drugs. We demonstrated that hypothyroid animals had a reduction in body weight and length, a retardation of neurodevelopment, and they had depressive-like behavior.

Methimazole-induced hypothyroidism causes alteration of the REDOX environment, oxidative stress, and hepatic damage; events not caused by hypothyroidism itself.

UNLABELLED: Our objective was to compare, over a time-course, markers of oxidative stress, the REDOX environment, and the antioxidant enzymatic system in the liver of rats with methimazole- or thyroidectomy-caused hypothyroidism. METHODS: We used 60 male Wistar rats divided into four groups: 1) the euthyroid, which received only tap water, 2) false thyroidectomy, which received the surgery and postoperative treatment, 3) thyroidectomy-caused hypothyroidism, which had the thyroid gland removed and a parathyroid reimplant, and 4) methimazole-caused hypothyroidism in rats that received 60 mg/kg/d of the antithyroid drug in drinking water. Five rats of the euthyroid and methimazole-caused hypothyroidism groups were killed at the end of the first, second, third, and fourth week after treatment, and five rats of false thyroidectomy and thyroidectomy-caused hypothyroidism groups were killed at the end of the second and eighth week after the surgical procedure. Each liver was removed and stored at -70 degrees C until oxidative stress, REDOX environment, and antioxidant enzymatic system markers were tested. We also made a histological study at the end of the treatment. RESULTS: The histological study revealed that only the methimazole-caused hypothyroidism caused cell damage. This damage is associated with an increase of oxidative stress markers that were not compensated for by the antioxidant system. The catalase activity is reduced and this allows H2O2-caused damage. In conclusion methimazole causes cell damage in the liver, whereas hypothyroidism per se does not cause hepatic-cell damage.

Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes: An animal model of neurodevelopmental psychopathological disorders.

Our aim was to investigate if neonatal bilateral administration of lidocaine into the ventral hippocampus would cause behavioral changes related to schizophrenia. A neonatal ventral-hippocampal lesion (nVH lesion) was made with lidocaine in Wistar male pups. Two groups were formed, the first received lidocaine (4 mug/0.3 muL) and the second an equal volume of vehicle. At day 35 and 56, both groups were tested for social contact, immobility caused by clamping the neck and dorsal immobility, locomotor activity in an open field, and tail flick (TF) latency after a painful heat stimulus. All animals were then killed. Coronal cuts (7 mum) of the brain were obtained and each brain section was stained with cresyl violet-eosin. The animals which received the nVH lesion with lidocaine had decreased social interaction at both ages. The rats with lesions, only at day 58 postnatal, increased their distance traveled and ambulatory time, with a decrease in their nonambulatory and reset time. The rats with lesions had a longer duration of immobility caused by clamping the neck and a longer dorsal immobility at both days 34 and 57 compared to control rats. The lidocaine-treated group spent less time to deflect the tail compared to the control group at postpubertal age. The neonatal bilateral administration of lidocaine into the ventral hippocampus caused some alterations, such as chromatin condensation, nucleolus loss, and cell shrinkage, but glial proliferation was not seen. Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes.

Lidocaine affects the redox environment and the antioxidant enzymatic system causing oxidative stress in the hippocampus and amygdala of adult rats.

AIMS: Our objective was to investigate if oxidative stress is involved in the neural damage caused by lidocaine. MAIN METHODS: Male Wistar rats were used. The control group received 0.9% saline ip and the treated group received a single 60 mg/kg lidocaine dose ip. On days 1, 2, 5, and 10 after dosing, ten rats were sacrificed and their brains were quickly removed. The amygdala and hippocampus were dissected. Five samples were used to determine lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG). Another five were used to measure antioxidant activities of glutathione peroxidase (GPX), catalase, Cu-Zn SOD (superoxide dismutase), Mn SOD, and total SOD. KEY FINDINGS: Ten days after injection of lidocaine, lipid peroxidation increases in the hippocampus because the ROS are enhanced from day 5, whereas in the amygdala lipid peroxidation and the ROS were enhanced only on the first day postinjection. Lidocaine causes an increased concentration of GSH and GSSG in the hippocampus from the first day. In the amygdala the GSH and GSSG content were increased at day 10. In the hippocampus the catalase activity was enhanced, whereas the total SOD and Cu-Zn SOD activities were decreased. In the amygdala the lidocaine enhances the activities of catalase and GPX, but no SOD isoenzymes were modified. SIGNIFICANCE: In this research we demonstrated that lidocaine affects the redox environment and promotes increases of the oxidative markers both in the hippocampus and amygdala but in a different pattern.

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats.

There is evidence that using lidocaine-treated cellular culture produces cell damage. However, there are no studies in vivo demonstrating the potential injurious effect of lidocaine on the central nervous system. Therefore, the aim of our study was to investigate if lidocaine is involved in neuronal damage in the CA3 hippocampus and amygdala regions when using a single subconvulsive or a convulsive lidocaine dose. Two-month-old male Wistar rats (57) were used. The animals were randomly assigned to one of three groups. Group I received 0.9% saline ip (n=9), group II received a single lidocaine dose of 60 mg/kg (n=18), and group III received 90 mg/kg ip (n=12). At day 2, 7, and 10 after the dosing, three to six rats per group were sacrificed. The brains of the rats were removed and were embedded in paraffin. Coronal cuts of 7 microm were made. Each brain section was stained with cresyl-eosin. We evaluated the number of normal and abnormal neurons in the hippocampal CA3 (pyramidal) and basolateral amygdala (large and medium neurons) regions in a 10,000 microm2 section. To explore an association between lidocaine-induced seizure and neuronal damage, diazepam was used (10 mg/kg ig) as an anticonvulsant two hours before a 90 mg/kg dose of lidocaine. Lidocaine causes a morphological neuronal alteration in the CA3 hippocampal region and the basolateral amygdala and possibly an inhibition-excitation imbalance. Diazepam prevents lidocaine-induced seizures, but not neuronal damage in brain structures. Interaction of lidocaine with the membrane components produces disrupted Ca+2 homeostasis and causes neuronal damage. Moreover, it is possible that lidocaine or its metabolites could actively participate in the neuronal damage observed.

Perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats.

The present study was developed to ascertain whether or not susceptibility to lidocaine-kindling persists into adulthood in perinatal hypothyroid rats. Pregnant Wistar rats were randomly divided into two groups: the first one, a control group, that drank tap water; and a second one, a hypothyroid group, were treated with 0.02% propylthiouracil in their drinking water from the 14th gestational day to the 10th postpartum day. The pups of both groups were maintained with food and tap water ad libitum until the experiment was over. The pups of each group were divided to test the susceptibility to lidocaine-kindling at 30 and 100 days old, for this, lidocaine (50 mg/kg, i.p.) was administered daily. The seizures were usually present in the form of tonic attacks of fore and hind limbs, followed by intermittent clonic movements. An animal was considered kindled when it showed clonic movements for two consecutive days. We observed that the number of stimuli necessary to produce lidocaine-kindling seizures in hypothyroid rats was significantly lower than in the control group for both ages. Also, the percentage of kindled rats aged 30 days (73% and 89%) was greater than aged of 100 days (26% and 59%) in both control and hypothyroid groups, respectively. In conclusion, the perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats.