Pontine and Cerebellar Norepinephrine Content in Adult Rats Recovering from Focal Cortical Injury

Norepinephrine (NE) plays an important role in motor recovery after brain damage. Most studies concerning NE activity have been performed in the cerebellum, while the role of the pons, the site where the norepinephrinergic locus coeruleus is located, has not yet been elucidated. For this work, we studied the changes in cerebellar and pontine NE content in sham-operated (n = 17), motor cortex injured (n = 6) and recovered rats (n = 12). Motor effects were assessed by means of footprint analysis and sensorimotor evaluation. It was found that after cortical brain damage, the stride length decreases while the stride angle increases after 6 h post-surgery, while the sensorimotor evaluation showed an increase in the motor deficit. Recovery was observed after 24 h. NE content increased in the pons after 6 h and returned to normal levels in recovered rats, with no significant changes observed in the cerebellum. Based on the functional remote inhibition, it is possible that NE exerts an autoinhibitory effect in the pons after motor cortical ablation. On the other hand, the absence of an effect in the cerebellum suggests that cerebellar NE activity related to damage and/or recovery is limited to discrete areas of the structure.     

Recovery of Motor Deficit,Cerebellar Serotonin and Lipid Peroxidation Levels in the Cortex of Injured Rats

The sensorimotor cortex and the cerebellum are interconnected by the corticopontocerebellar (CPC) pathway and by neuronal groups such as the serotonergic system. Our aims were to determine the levels of cerebellar serotonin (5-HT) and lipid peroxidation (LP) after cortical iron injection and to analyze the motor function produced by the injury. Rats were divided into the following three groups: control, injured and recovering. Motor function was evaluated using the beam-walking test as an assessment of overall locomotor function and the footprint test as an assessment of gait. We also determined the levels of 5-HT and LP two and twenty days post-lesion. We found an increase in cerebellar 5-HT and a concomitant increase in LP in the pons and cerebellum of injured rats, which correlated with their motor deficits. Recovering rats showed normal 5-HT and LP levels. The increase of 5-HT in injured rats could be a result of serotonergic axonal injury after cortical iron injection. The LP and motor deficits could be due to impairments in neuronal connectivity affecting the corticospinal and CPC tracts and dysmetric stride could be indicative of an ataxic gait that involves the cerebellum.     

Prenatal Exposure to Ozone Disrupts Cerebellar Monoamine Contents in Newborn Rats

Ozone (O3) is widely distributed in environments with high levels of air pollution. Since cerebellar morphologic disruptions have been reported with prenatal O3 exposure, O3 may have an effect on some neurotransmitter systems, such as monoamines. In order to test this hypothesis, we used 60 male rats taken from either, mothers exposed to 1 ppm of O3 during the entire pregnancy, or from mothers breathing filtered and clean air during pregnancy. The cerebellum was extracted at 0, 5, and 10 postnatal days. Tissues were processed in order to analyze by HPLC, dopamine (DA) levels, 3,4 dihydroxyphenilacetic acid (DOPAC) and homovanillic acid (HVA), norepinephrine (NA), serotonin, and 5-hydroxy-indole-acetic acid (5-HIAA) contents. Results showed a decrease of DA, NA, DOPAC and HVA mainly in 0 and 5 postnatal days. There were no changes in 5-HT levels, and 5-HIAA showed an increase after 10 postnatal days. DOPAC + HVA/DA ratio showed changes in 0 and 10 postnatal days, while 5-HIAA/5-HT ratio showed a slight decrease in 0 days. The data suggest that prenatal O3 exposure disrupts the cerebellar catecholamine system rather than the indole-amine system. Disruptions in cerebellar NA could lead to ataxic symptoms and also could limit recovery after cortical brain damage in adults. These finding are important given that recovery mechanisms observed in animals are also observed in humans.     

Acute administration of levetiracetam in tonic pain model modulates gene expression of 5HT1A and 5HT7 receptors in the thalamus of rats (Rattus norvergicus)

The nociceptive effect of Levetiracetam (LEV) on the expression of 5-HT_1A and 5-HT₇ receptors found in the thalamus was evaluated. Thirty-six male rats (Wistar) were randomized into six groups: in the Control group without treatment; LEV50 group LEV was administered in a single dose of 50 mg/kg i.g.; in the LEV300 group LEV dose of 300 mg/kg i.g.; in the FORMALIN group the formalin test was performed; in the LEV50/FORMALIN group LEV dose of 50 mg/kg i.g and the formalin test was performed; in the LEV300/FORMALIN group LEV dose of 300 mg/kg i.g and the formalin test was performed, subsequently the thalamus was dissected in all groups. In the formalin tests LEV exhibited an antinociceptive effect in the LEV300/FORMALIN group (p?<?0.05) and a pronociceptive effect in the LEV50/FORMALIN group (p?<?0.001). The results obtained by Real-time PCR confirmed the expression of the 5-HT_1A and 5-HT₇ receptors in the thalamus, 5-HT_1A receptors increased significantly in the FORMALIN group and the LEV300/FORMALIN group (p?<?0.05). 5-HT7 receptors are only over expressed at a dose of 300 mg/Kg of LEV with formalin (p?<?0.05). This suggests that LEV modulates the sensation of pain by controlling the expression of 5-HT_1A and 5-HT₇ in a tonic pain model, and that changes in the expression of 5-HT_1A and 5-HT₇ receptors are associated with the sensation of pain, furthermore its possibility to be used in clinical treatments for pain.

     

The Selective Inhibition of the D1 Dopamine Receptor Results in an Increase of Metabolized Dopamine in the Rat Striatum

Our aim was to study the specific role of the postsynaptic D(1) receptors on dopaminergic response and analyze the metabolized dopamine (DA) in the rat striatum. We used male Wistar rats to evaluate the effects of different doses of a D(1) agonist (SKF-38393) and a D(1) antagonist (SCH-23390), and their co-administration. The levels of DA and L-3, 4-dihydroxyphenylacetic acid (DOPAC) were measured using high performance liquid chromatography. The systemic injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter the DA and DOPAC levels or the DOPAC/DA ratio. In contrast, injection of SCH-23390 alone at 0.25, 0.5 and 1 mg/kg significantly increased the DA and DOPAC levels, as well as the DOPAC/DA ratio, compared with the respective control groups. The co-administration of SCH-23390+SKF-38393 did not alter the DA or DOPAC levels, but it did significantly inhibit the SCH-23390-induced increase of the DA and DOPAC levels. The SCH-23390+SKF-38393 and the SCH-23390-only groups showed an increase in the DOPAC/DA ratio. The co-administration of SCH-23390+PARGYLINE significantly decreased the DOPAC levels and the DOPAC/DA ratio compared with the control and SCH-23390 groups. Taken together, our results showed that selective inhibition with SCH-23390 produced an increase in metabolized DA via striatal monoamine oxidase. These findings also contribute to the understanding of the role of postsynaptic D(1) receptors in the long-loop negative feedback system in the rat striatum.