Efeito do lítio sobre a hiperatividade locomotora induzida pela lesão eletrolítica da região do núcleo mediano da rafe em ratos

A lesão do núcleo mediano da rafe (NMR) produz sintomas que sugerem validade de face ao episódio maníaco. Esta pesquisa avaliou o efeito do lítio sobre a hiperatividade locomotora induzida por esta lesão. Vinte e um ratos Wistar machos foram submetidos à lesão eletrolítica da região do NMR (LR) e 17 foram submetidos à lesão fictícia (LF). Após recuperação, a atividade locomotora foi avaliada na caixa de atividade (Med Associates/ENV-515). Parte dos animais destes grupos recebeu tratamentos com lítio (47,5 mg/kg/2x dia i.p.) por 10 dias, enquanto o restante foi tratado com salina no mesmo esquema. A reavaliação ao final dos tratamentos demonstrou que o lítio reduziu significantemente a atividade locomotora em relação à avaliação inicial no grupo LR (ANOVA/Bonferroni p < 0,05), tornando-a equivalente aos baixos níveis dos grupos LF. Estes dados sustentam a hipótese de que as manifestações induzidas pela lesão do NMR podem constituir um modelo animal de mania.

Developmental lead exposure: behavioral alterations in the short and long term

Wistar dams were exposed to 500 ppm of Pb, as Ph acetate, or 660 ppm Na acetate in drinking water during pregnancy and lactation. Male pups at 23 (weaned) or 70 days (adult) of age were submitted to behavioral evaluation and Pb determination. The behaviors evaluated were: locomotor activity (open-field test), motor coordination (rotarod test), exploratory behavior (holeboard test), anxiety (elevated plus maze and social interaction tests), and learning and memory (shuttle box). Ph levels were measured in the blood and cerebral regions (hippocampus and striatum) of dams and pups. The results of the present report demonstrated that exposure to Ph during pregnancy and lactation induces in weaned pups hyperactivity, decreased exploratory behavior, and impairment of learning and memory. These alterations were observed at blood Ph levels in the range that may be attained in children chronically exposed to low levels of Pb (21 +/- 3 mug/dl). Regarding adults, the results demonstrated that the regimen of exposure adopted induces anxiety in these animals at nondetectable blood Ph levels. (C) 2001 Elsevier B.V. All rights reserved.

Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP. (C) 2003 Elsevier B.V. (USA). All rights reserved.

Developmental lead exposure in rats: is a behavioral sequel extended at F2 generation?

Lead toxicity was studied in rats exposed from conception until weaning and assessed by monitoring offspring behavior in both the open field and elevated plus maze and by determining tissue lead in an assessment schedule extended to first (F1) and second (F2) generations. Dams utilized for the F1 generation were submitted to 750 ppm of lead (acetate) in drinking water during pregnancy and lactation. For F1 pups, behavioral alterations were not detected in the elevated plus maze, while in the open field, spontaneous locomotor activity as well as time of both grooming and rearing increased, while freezing time decreased in 30- and 90-day-old rats. Lead content was higher in tissues of 1- and 30-day-old pups. However, in 90-day-old rats, lead was detected only in the femur. F2 generation was lead-free but still presented alterations in both locomotor activity and grooming in 30- and 90-day-old pups. It appears that developmental lead exposure may cause behavioral effects during the developmental stage of the F1 generation, which remains throughout the animal's adult life as a sequel, regardless of lead accumulation, and is extended to the F2 generation of rats. (C) 2001 Elsevier B.V. All rights reserved.

Regulation of contextual conditioning by the median raphe nucleus

The median raphe nucleus (MRN) has been suggested as the origin of a behavioral inhibition system that projects to the septum and hippocampus. Electrical stimulation of this mesencephalic area causes behavioral and autonomic manifestations characteristic of fear such as, freezing, defecation and micturition. In this study we extend these observations by analyzing the behavioral and autonomic responses of rats with lesions in the MRN submitted to a contextual conditioning paradigm. The animals underwent electrolytic or sham lesions of the median raphe nucleus. One day (acute) or 7 days (chronic) later they were tested in an experimental chamber where they received 10 foot-shocks (0.7 mA, 1 s with 20-s interval). The next day, sham and MRN-lesioned animals were tested again either in the same or in a different experimental chamber. During this, the duration of freezing, rearings, bouts of micturition and number of fecal boli were recorded. Sham-operated rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly suppressed in rats with acute or chronic lesions in the MRN. MRN lesions also reduced the bouts of micturition and number of fecal boli. These rats showed a reduced number of rearings than sham-lesioned rats. This effect is probably the result of the displacement effect provoked by freezing since no significant differences in the number of rearings could be observed between these animals and the NMR-lesioned rats tested in an open field. This lesion produced higher horizontal locomotor activity in this test than the controls (sham-lesioned rats). These results point to the importance of the median raphe nucleus in the processing of fear conditioning with freezing being the most salient feature of it. Behavioral inhibition is also under control of MRN but its neural substrate seems to be dissociated from that of contextual fear. (C) 1998 Elsevier B.V. B.V.

Plant derived alkaloid (-)-cassine induces anti-inflammatory and anti-hyperalgesics effects in both acute and chronic inflammatory and neuropathic pain models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Implication of the 5-HT(2A) and 5-HT(2C) (but not 5HT(1A)) receptors located within the periaqueductal gray in the elevated plus-maze test-retest paradigm in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Contrasting effects of acute and chronic treatment with imipramine and fluoxetine on inhibitory avoidance and escape responses in mice exposed to the elevated T-maze

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Similar anxiolytic-like effects following intra-amygdala infusions of benzodiazepine receptor agonist and antagonist: Evidence for the release of an endogenous benzodiazepine inverse agonist in mice exposed to elevated plus-maze test

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice

Glutamate-NMDA (N-methyl-D-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g. jumping and running) and antinociception induced by intra-PAG injection of N-methyl-D-aspartate (NMDA) were completely blocked by prior infusion of N(omega)-propyl-L-arginine (NPLA), a specific neuronal nitric oxide synthesis (nNOS) enzyme inhibitor, into the same midbrain structure. It remains unclear however, whether the inhibition of nNOS within the mouse PAG changes the anxiety-like behavior per se or the effects of the inhibition of nNOS depend on the suppression of downstream of glutamate-NMDA receptor activation. This study investigated whether intra-PAG infusion of NPLA (i) attenuates anxiety in the elevated plus-maze (EPM) and (ii) antagonizes the anxiogenic-like effects induced by intra-PAG injection of NMDA. Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that intra-PAG infusions of NPLA (0.2, 0.4 or 0.8 nmol/0.1 mu l) did not alter significantly any behavioral response in the EPM when compared to control group (Experiment 1). Intra-PAG infusion of NMDA (0 and 0.02 nmol/0.1 mu l; a dose that does not provoke vigorous defensive behaviors per se in mice) significantly reduced open arm exploration, confirming an anxiogenic-like effect (Experiment 2). When injected into the PAG 10 min prior local NMDA injection (0.02 nmol/0.1 mu l), NPLA (0.4 nmol/0.1 mu l) was able to revert the anxiogenic-like effect of glutamate-NMDA receptor activation. Neither intra-PAG infusion of NMDA nor NPLA altered closed arm entries, a widely used measure of locomotor activity in the EPM. These results suggest that intra-PAG nitric oxide synthesis does not play a role on anxiety-like behavior elicited during EPM exposure; however its synthesis is important for the proaversive effects produced by activation of glutamate-NMDA receptors located within this limbic midbrain structure. (C) 2008 Elsevier B.V. All rights reserved.

Ventrolateral periaqueductal gray lesion attenuates nociception but does not change anxiety-like indices or fear-induced antinociception in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reinforcing properties of fencamfamine: Involvement of dopamine and opioid receptors

Fencamfamine (FCF) is a psychostimulant classified as an indirect dopamine agonist. The conditioning place preference (CPP) paradigm was used to investigate the reinforcing properties of FCF. After initial preferences had been determined, animals were conditioned with FCF (1.75, 3.5, or 7.0 mg/kg; IP). Only at the dose of 3.5 mg/kg FCF produced a significant place preference. Pretreatment with SCH23390 (0.05 mg/kg, SC) or naloxone (1.0 mg/kg SC) 10 min before FCF (3.5 mg/kg; IP) blocked both FCF-induced hyperactivity and CPP. Pretreatment with metoclopramide (10.0 mg/kg; IP) or pimozide (1.0 mg/kg, IP), respectively, 30 min or 4 h before FCF (3.5 mg/kg; IP), which blocked the FCF-induced locomotor activity, failed to influence place conditioning produced by FCF. In conclusion, the present study suggests that dopamine D 1 and opioid receptors are related to FCF reinforcing effect, while dopamine D 2 subtype receptor was ineffective in modifying FCF-induced CPP.

Acute, subchronic and chronic 2,4-dichlorophenoxyacetic acid (2,4-D) intoxication in rats

The acute, subchronic and chronic toxicities of 2,4- dichlorophenoxyacetic acid (2,4-D) were studied in rats. Animals were exposed acutely (600 mg/kg), subchronically (200 ppm for 30 d) and chronically (200 ppm for 180 d) to 2,4-D by the oral route. Clinical, laboratory and histopathological methods were used as indicators of toxicity. After acute exposure, the herbicide decreased locomotor activity and induced ataxia, sedation, muscular weakness (mainly of the hind quarters) and gasping for breath; increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), amylase activities and creatinine levels; decreased total protein (TP) and glucose levels; and increased hematocrit values. Subchronic and chronic 2,4-D exposures did not induce overt clinical signs or symptoms of intoxication. However, subchronic herbicide exposure increased AST activity and albumin and hematocrit values, and chronic exposure increased AST, AP and LDH activities, decreased amylase and glucose levels, but did not change hematocrit values. Chromatographic analysis of the serum of chronically exposed rats showed the presence of the herbicide; the amount found (3.76 ± 1.16 mg/ml) suggested the absence of 2,4-D accumulation within the body. Although macroscopic or histopathological lesions were not observed in acutely, subchronically or chronically 2,4-D exposed rats, the laboratory data obtained suggest tissue injuries after dosing, since the results are considered early indicators of primarily hepatic and muscle tissue damage.

Envolvimento do sistema dopaminérgico na sensibilização comportamental ao femproporex

The effects of repeated administration of fenproporex (FEN) on motor activity of rats were studied. FEN-treated group (5.0 mg/kg, i.p., single dose, 7 consecutive days), showed a marked increase in the motor activity of rats, indicating that the drug induced behavioral sensitization. Repeated coadministration of haloperidol prevented the development of sensitization to repeated administration of FEN. Repeated administration of FEN increased also locomotor activity measured in the open field, ratifying the occurence of sensitization. These findings indicated development of sensitization to repeated FEN administration and that the dopamine system might be involved in the mechanism of sensitization.

Baseline and stress-induced plasma corticosterone concentrations of mice selectively bred for high voluntary wheel running

The hypothalamic-pituitary-adrenal (HPA) axis is important in regulating energy metabolism and in mediating responses to stressors, including increasing energy availability during physical exercise. In addition, glucocorticoids act directly on the central nervous system and influence behavior, including locomotor activity. To explore potential changes in the HPA axis as animals evolve higher voluntary activity levels, we characterized plasma corticosterone (CORT) concentrations and adrenal mass in four replicate lines of house mice that had been selectively bred for high voluntary wheel running (HR lines) for 34 generations and in four nonselected control (C) lines. We determined CORT concentrations under baseline conditions and immediately after exposure to a novel stressor (40 min of physical restraint) in mice that were housed without access to wheels. Resting daytime CORT concentrations were approximately twice as high in HR as in C mice for both sexes. Physical restraint increased CORT to similar concentrations in HR and C mice; consequently, the proportional response to restraint was smaller in HR than in C animals. Adrenal mass did not significantly differ between HR and C mice. Females had significantly higher baseline and postrestraint CORT concentrations and significantly larger adrenal glands than males in both HR and C lines. Replicate lines showed significant variation in body mass, length, baseline CORT concentrations, and postrestraint CORT concentrations in one or both sexes. Among lines, both body mass and length were significantly negatively correlated with baseline CORT concentrations, suggesting that CORT suppresses growth. Our results suggest that selection for increased locomotor activity has caused correlated changes in the HPA axis, resulting in higher baseline CORT concentrations and, possibly, reduced stress responsiveness and a lower growth rate. © 2007 by The University of Chicago. All rights reserved.