The role of magnesium sulfate in prevention of seizures induced by pentylenetetrazole in rats / O papel do sulfato de magnésio na prevenção de crises induzidas por pentilenotetrazol em ratos

Magnesium sulfate (MgSO4) has been used to prevent seizures in eclampsia. This study examined the central effects of MgSO4 on different types of pentylenetetrazole (PTZ)-induced seizures. Male Wistar rats were submitted to intracerebroventricular (ICV) administration of MgSO4 at different doses followed by intraperitoneal administration of PTZ. The latency to the onset of the first seizure induced by PTZ was significantly increased by ICV administration of MgSO4 at a dose of 100 µg compared to the control treatment. In addition, the total period during which animals presented with seizures was significantly reduced at this dose of MgSO4. Furthermore, the latency to the onset of the first partial complex seizure was significantly increased by the lowest dose of MgSO4. However, a high dose of MgSO4 had no effect or even potentiated the effect of PTZ. These results suggest that, depending on the dose, MgSO4 may be important in prevention of epileptic seizures.

Sulfato de magnésio (MgSO4) é utilizado para prevenir crises epilépticas na eclampsia. Este estudo examina os efeitos do MgSO4 em diferentes tipos de crise induzidas por pentilenotetrazol (PTZ). Ratos Wistar foram submetidos à administração intracerebroventricular (ICV) de diferentes doses de MgSO4 seguida de administração intraperitoneal de PTZ. A latência para o início da primeira crise induzida por PTZ foi aumentada pela administração ICV de MgSO4 na dose de 100 µg quando comparada ao tratamento controle. Além disso, o período durante o qual os animais apresentaram crises foi reduzido com a mesma dose de MgSO4. A latência para o início da primeira crise parcial complexa também foi aumentada com a dose menor de MgSO4 (32 µg). No entanto, a maior dose (320 µg) de MgSO4 não foi efetiva ou até potencializou os efeitos do PTZ. Esses resultados sugerem que, dependendo da dose, o MgSO4 pode ser útil na prevenção de crises epilépticas.

Organization of electrically and chemically evoked defensive behaviors within the deeper collicular layers as compared to the periaqueductal gray matter of the rat.

Stimulation of the periaqueductal gray matter (PAG) and the deeper layers of superior colliculus (SC) produces both freezing (tense immobility) and flight (trotting, galloping and jumping) behaviors along with exophthalmus (fully opened bulging eyes) and, less often, micturition and defecation. The topography of these behaviors within the distinct layers of SC remains unclear. Therefore, this study compared the defensive repertoire of intermediate (ILSC) and deep (DLSC) layers of SC to those of dorsolateral periaqueductal gray matter (DLPAG) and lateral periaqueductal gray matter (LPAG) [Neuroscience 125 (2004) 71]. Electrical stimulation was carried out through intensity- (0-70 microA) and frequency-varying (0-130 Hz) pulses. Chemical stimulation employed a slow microinfusion of N-methyl-d-aspartic acid (NMDA, 0-2.3 nmol, 0.5 nmol/min). Probability curves of intensity-, frequency- and NMDA-evoked behaviors, as well as the unbiased estimates of median stimuli, were obtained by threshold logistic analysis. Compared with the PAG, the most important differences were the lack of frequency-evoked jumping in both layers of SC and the lack of NMDA-evoked galloping in the ILSC. Moreover, although galloping and jumping were also elicited by NMDA stimulation of DLSC, effective doses were about three times higher than those of DLPAG, suggesting the spreading of the injectate to the latter structure. In contrast, exophthalmus, immobility and trotting were evoked throughout the tectum structures. However, whatever the response and kind of stimulus, the lowest thresholds were always found in the DLPAG and the highest ones in the ILSC. Besides, neither the appetitive, nor the offensive, muricide or male reproductive behaviors were produced by any kind of stimulus in the presence of appropriate targets. Accordingly, the present data suggest that the deeper layers of SC are most likely involved in the increased attentiveness (exophthalmus, immobility) or restlessness (trotting) behaviors that herald a full-blown flight reaction (galloping, jumping) mediated in the PAG.

Effects of the cannabinoid ligand SR 141716A alone or in combination with delta9-tetrahydrocannabinol or scopolamine on learning in squirrel monkeys.

To investigate the effects of the cannabinoids on learning and on scopolamine-induced disruptions in learning, delta9-tetrahydrocannabinol (delta9-THC), SR 141716A (an antagonist at CB1 receptors) and scopolamine were administered to squirrel monkeys responding in a repeated-acquisition task. In this task, monkeys acquired a different three-response sequence each session and responding was maintained by food presentation under a second-order fixed-ratio 5 schedule. When either delta9-THC (0.1-0.56 mg/kg, i.m.) or SR 141716A (1-10 mg/kg, i.m.) was administered alone, 60 and 75 min before the session, respectively, both cannabinoid ligands dose-dependently decreased the overall rate of responding and increased the overall percentage of errors. However, at a dose that had little or no effect alone (i.e. 1 mg/kg), SR 141716A antagonized the disruptive effects of delta9-THC (0.18-1.8 mg/kg) on acquisition, shifting the dose-effect curves for rate of responding and percentage of errors at least 1/2 log unit to the right. Finally, when either delta9-THC (0.001-1 mg/kg) or SR 141716A (0.32-10 mg/kg) was administered with scopolamine (0.01 or 0.032 mg/kg, 15 min before the session), greater rate-decreasing and error-increasing effects were obtained than with scopolamine alone. These results suggest that while low doses of SR 141716A can antagonize the effects of delta9-THC in squirrel monkeys, high doses can also disrupt acquisition when administered alone and potentiate the disruptive effects of scopolamine on acquisition.

Effects of diazepam or haloperidol on convulsion and behavioral responses induced by bilateral electrical stimulation in the medial prefrontal cortex.

1. Effects of diazepam (DZP) or haloperidol (HAL) on convulsions and behavioral responses (locomotion, circling, spying and head shaking) induced by bilateral electrical stimulation in the medial prefrontal cortex (mPFC) were examined. 2. Male Wistar rats were electrically stimulated (ten 30-sec trains, 60 Hz, 80-100 microA) bilaterally in the mPFC and their behavior was simultaneously observed in an open field in daily session. 3. DZP and HAL dose-response curves (0, 0.5, 1.25, 2.5 and 5 mg/kg, i.p., 30 min before electrical stimulation session) were determined after a baseline of behavioral responses was established. 4. DZP dose-dependently decreased head shaking and convulsions, had no effect in circling and spying behaviors, and increased locomotion except at the highest dose. HAL reduced locomotion, circling and spying behaviors in a dose-dependent manner, but did not affect convulsions or head shaking. 5. These results demonstrated that convulsion and behavioral responses induced by electrical activation of the mPFC were modified by DZP or HAL. Therefore, the mPFC is involved in the mediation of neural and/or behavioral activity that may be implicated in some central effects of psychoactive drugs.

Alcohol dependence induced in rats by semivoluntary intermittent intake

The objetive of the present experiment was to assess ethyl alcohol (ETOH) dependence brought about by a semivoluntary intermittent intake regimen in rats. Male Wistar rats weighing 150-250 g at the onset of the experiment were assigned to the following groups: 0 percent ETOH (N = 11), 5 percent ETOH (N = 20), 20 percent ETOH (N = 20) and 40 percent ETOH (N = 18). ETOH solutions were offered at the end of the day and overnight from Monday to Friday, and throughout weekends, for 90 days. The concentration of the ETOH solutions was increased in a stepwise fashion allowing the rats to get used to the taste of alcohol. Reposition of pure water was permitted during 1-h water drinking periods in the morning. Daily volume intake (+ SEM) averaged 25.4 + 0.4 ml (0 percent ETOH), 23.8 + 0.6 ml (5 percent ETOH), 17.6 + 0.7 ml (20 percent ETOH) and 17.5 + 0.6 ml (40 percent ETOH). ETOH consumption differed significantly (P<0.05) among groups, averaging 4.4 + 0.2 g Kg(-1) day(-1) (5 percent ETOH), 10.3 + 0.3 g Kg(-1) day(-1) (20 percent ETOH) and 26 + 1.2 g kg(-1) day(-1) (40 percent ETOH). Furthermore, ETOH detection in plasma 10-12h after offering the solution indicated that its consumption in the 40 percent ETOH group was sufficient to override its metabolism. Overt signs of ETOH dependence, such as increased thirst, hyperactivity, puffing, hair ruffling and startle responsiveness as well as reduced drowsiness, were significantly increased in the 20 percent and 40 percent ETOH groups compared to the 0 percent and 5 percent groups. Accordingly, the model described here proved to be a useful tool for the evaluation of subtle or moderate behavioral and physical consequences of long-term ETOH intake.

Effects of acute daily administration of diazepam on spatial learning and working memory.

This study evaluated the acute or daily effects of diazepam (DZP) on the acquisition and performance of rats in an 8-arm radial maze. Male Wistar rats (200-250 g) were divided into three groups: saline-saline (SS), saline-DZP (SD) and DZP-DZP (DD). The SS group always received intraperitoneal (i.p.) saline (SAL) in daily or acute treatments. The SD group received SAL (i.p.) daily during the task acquisition (30 days), DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests, and it also received DZP (10 mg/kg, i.p.) for 70 days. The DD group received DZP (10 mg/kg, i.p.) daily during 30 days in the task acquisition, DZP (2.5 mg/kg, i.p.) 45 min before the acute 5 s and 1 h delay tests and further received DZP (10 mg/kg, i.p.) for an additional 70 days. Our results showed that as compared to control (SS group), 8-10 h prior administration of a single daily dose of DZP (10 mg/kg) did not alter the learning and the performance of short- (5 s delay) and long-term (1 h delay) working memory. However, the acute administration of DZP (2.5 mg/kg) impaired the performance of the short delay task (5 s delay) in animals previously exposed (DD group) or not (SD group) to daily DZP treatment. Therefore, the acute administration of an anxiolytic dose of DZP (2.5 mg/kg) produced a significant impairment of short-term working memory, even in animals exposed to daily DZP treatment for a long time.

[Effects of chronic administration of alcohol on neural mechanisms of arterial blood pressure regulation]. / Efeitos da administração crônica do álcool sobre os mecanismos neurais de regulação da pressão arterial.

PURPOSE: This study evaluated the effect of alcohol and its withdrawal on arterial baroreflex (BR) and cardiopulmonary reflex (CPR). METHODS: Male Wistar rats (150-250g) distributed in three groups (10-19 animals in each): ETOH 0%, ETOH 5% and ETOH 20%, received alcohol solution at the end of the day and at night over the week, and all day and night at the weekends for a 90 day period. The BR function was assessed analyzing the bradycardic response to phenylephrine-induced vasoconstriction and tachycardic response to sodium nitroprusside-induced vasodilatation. The CPR was evaluated through the simultaneous bradycardic and hypotensive responses to 5-hydroxytryptamine (5-HT). The tests were performed in conscious animals in conditions of alcohol intake or 48h alcohol withdrawal. RESULTS: The nonwithdrawn animals of ETOH 5% group showed significative decrease of mean arterial pressure compared to ETOH 0% and an increase of heart rate compared to ETOH 0% and 20% groups. The sensitivity (gain) of baroreceptor reflex was significantly attenuated in ETOH 5% withdrawn animals and in ETOH 5% and 20% animals nonwithdrawn. This was mainly due to the reduction of range of the baroreflex and changes in the bradycardia and tachycardia plateau. The nonwithdrawn ETOH 5% group showed a higher effect of 5-HT (around 50%) on the fall of diastolic arterial pressure. CONCLUSION: These results suggest that alcohol intake produced significant alterations in the neural mechanisms of cardiovascular regulation that could result in a dysfunction of blood pressure regulation.

Efeitos da administração crônica do álcool sobre os mecanismos neurais de regulação da pressão arterial / Effect of Chronic Administration of Alcohol and its Withdrawal on the Neural Mechanisms of Arterial Blood Pressure Regulation

PURPOSE: This study evaluated the effect of alcohol and its withdrawal on arterial baroreflex (BR) and cardiopulmonary reflex (CPR). METHODS: Male Wistar rats (150-250g) distributed in three groups (10-19 animals in each): ETOH 0, ETOH 5and ETOH 20, received alcohol solution at the end of the day and at night over the week, and all day and night at the weekends for a 90 day period. The BR function was assessed analyzing the bradycardic response to phenylephrine-induced vasoconstriction and tachycardic response to sodium nitroprusside-induced vasodilatation. The CPR was evaluated through the simultaneous bradycardic and hypotensive responses to 5-hydroxytryptamine (5-HT). The tests were performed in conscious animals in conditions of alcohol intake or 48h alcohol withdrawal. RESULTS: The nonwithdrawn animals of ETOH 5group showed significative decrease of mean arterial pressure compared to ETOH 0and an increase of heart rate compared to ETOH 0and 20groups. The sensitivity (gain) of baroreceptor reflex was significantly attenuated in ETOH 5withdrawn animals and in ETOH 5and 20animals nonwithdrawn. This was mainly due to the reduction of range of the baroreflex and changes in the bradycardia and tachycardia plateau. The nonwithdrawn ETOH 5group showed a higher effect of 5-HT (around 50) on the fall of diastolic arterial pressure. CONCLUSION: These results suggest that alcohol intake produced significant alterations in the neural mechanisms of cardiovascular regulation that could result in a dysfunction of blood pressure regulation.

Alcohol dependence induced in rats by semivoluntary intermittent intake.

The objective of the present experiment was to assess ethyl alcohol (ETOH) dependence brought about by a semivoluntary intermittent intake regimen in rats. Male Wistar rats weighing 150-250 g at the onset of the experiment were assigned to the following groups: 0% ETOH (N = 11), 5% ETOH (N = 20), 20% ETOH (N = 20) and 40% ETOH (N = 18). ETOH solutions were offered at the end of the day and overnight from Monday to Friday, and throughout weekends, for 90 days. The concentration of the ETOH solutions was increased in a stepwise fashion allowing the rats to get used to the taste of alcohol. Reposition of pure water was permitted during 1-h water drinking periods in the morning. Daily volume intake (+/- SEM) averaged 25.4 +/- 0.4 ml (0% ETOH), 23.8 +/- 0.6 ml (5% ETOH), 17.6 +/- 0.7 ml (20% ETOH) and 17.5 +/- 0.6 ml (40% ETOH). ETOH consumption differed significantly (P < 0.05) among groups, averaging 4.4 +/- 0.2 g kg-1 day-1 (5% ETOH), 10.3 +/- 0.3 g kg-1 day-1 (20% ETOH) and 26 +/- 1.2 kg-1 day-1 (40% ETOH). Furthermore, ETOH detection in plasma 10-12 h after offering the solution indicated that its consumption in the 40% ETOH group was sufficient to override its metabolism. Overt signs of ETOH dependence, such as increased thirst, hyperactivity, puffing, hair ruffling and startle responsiveness as well as reduced drowsiness, were significantly increased in the 20% and 40% ETOH groups compared to the 0% and 5% groups. Accordingly, the model described here proved to be a useful tool for the evaluation of subtle or moderate behavioral and physical consequences of long-term ETOH intake.

Effects of haloperidol on behavioral responses induced by electrical stimulation of medial prefrontal cortex.

The effects of haloperidol on circling and spying behaviors induced by electrical stimulation of the medial prefrontal cortex (PFC) were evaluated. Male Wistar rats with an electrode implanted into the left medial PFC (B: 2.5 mm A, 0.6 mm L and 2.7 mm V) were electrically stimulated in a sequence of ten 30-sec trains separated by 30-sec intervals (60 Hz) in each session, and simultaneously observed in the open field. The animals with circling (CI) and spying (SP) behaviors were treated with intraperitoneal haloperidol (HAL ip, 5 mg/kg, N = 6) and saline (SAL ip, N = 7) or intracortical HAL (ic, 5 micrograms, N = 6) and SAL (ic, N = 9), 20 min before the session of electrical stimulation. HAL ic significantly decreased (P < 0.05) CI (mean frequency +/- SEM: 0.5 +/- 0.16) and nonsignificantly decreased SP behavior (0.6 +/- 0.17) compared to SAL ic (CI: 0.9 0.02, SP: 1 +/- 0). HAL ip full abolished these behaviors (P < 0.05) (CI: 0.02 +/- 0, SP: 1 +/- 0) compared to SAL ip (CI: 0.86 +/- 0.06, SP: 0:93 +/- 0.06). These results show that haloperidol, a dopaminergic antagonist and antipsychotic agent, interfered significantly with the expression of behaviors induced by electrical stimulation of the left medial PFC, suggesting that the induction of these behaviors may involve the dopaminergic neurotransmission.

Effects of haloperidol on behavioral responses induced by electrical stimulation of medial prefrontal cortex

The effects of haloperidol on circling and spying behaviors induced by electrical simulation of the medial prefrontal cortex (PFC) were evaluated. Male Wistar rats with an electrode implanted into the left medial PFC (B:2.5 mmA, 0.6 mm L and 2.7 mm V) were electrically stimulated in a sequence of ten 30-sec trains separeted by 30-sec intervals (60 Hz) in each session, and simultaneously observed in the open field. The animals with circling (CI) and spying (SP) behaviors were treated with intraperitoneal haloperidol (HAL ip, 5 mg/Kg, N=6) and saline (SAL ip, N=7) or intracortical HAL (ic, 5 mug, N=6) and SAL (ic, N=9), 20 min before the session of eletrical stimulation. HAL ic significantly decreased (p<0.05) CI (mean frequency+ SEM: 0.5 + 0.16) and monsignificantly decreased SP behavior (0.6 + 0.17) compared to SAL ic (CI:0.9 + 0.02, SP: 1+ 0). HAL ip fully abolished these behaviors P<0.05) (CI:0.02 + 0,SP: 0.01 + 0) compared to SAL ip (CI: 0.86 + 0.06, SP: 0.93 + 0.06. These results show that haloperidol, a dopaminergic antagonist and antipsychotic agent, interfered significantly with the expression of behaviors induced by electrical stimulation of the left medial PFC, suggesting that the induction of these behaviors may involve the dopaminergic neurotransmission.

Deficits of spatial learning and working memory in spontaneously hypertensive rats.

It is possible that behavioral dysfunction, including cognitive, perceptual and psychomotor impairments in hypertensive subjects, can be the result of the high blood pressure. The aim of this study was to evaluate the performance of the spontaneously hypertensive rats (SHR) in the acquisition and execution of tasks in an 8-arm radial maze. Male Wistar normotensive rats (CON, n = 11) and SHR (n = 12), 3 months old, were first submitted to a series of training sessions to enter each of the 8 arms once in a given session (task acquisition), and errors (revisiting an arm in the same session) were computed. Errors before and after two delay intervals (5 s and 1 h, introduced between the fourth and fifth arm choice) were measured. These delayed tests allowed us to evaluate the working memory in different terms. It was observed that the SHR group made slightly more errors during the acquisition sessions and in the execution of the post-delay of 5-s interval tests, and significantly in the execution of the post-delay of 1-h interval tests compared to the CON. These results show that the SHR has a deficiency in the performance of the radial maze, suggestive of impairment of learning and working memory, mainly for a long-term memory, corroborating the hypothesis about the possible behavioral consequences of hypertension.

Effect of age and magnesium administration on the performance of SHR in the elevated plus-maze.

It is currently accepted that young spontaneously hypertensive rats (SHR) have lower pressure levels than adult SHR in which the hypertension is well established, reaching the highest plateau at about 24 weeks, and that treatment with magnesium initiated during intrauterine life postpones the onset of cardiovascular alterations in SHR to about 90 days. These animals also show many behavioral alterations. The anxiety of SHR was measured in the elevated plus-maze, considering the age of the animals and previous ingestion of food supplemented with 1% magnesium oxide. Both young (1.5-2 months) and adult (5-6 months) SHR showed higher mean ( +/- SEM) percent of entries (48 +/- 3 and 51 +/- 3, respectively) and a longer mean ( +/- SEM) percent of time spent (43 +/- 5 and 55 +/- 5, respectively) in the open arms when compared to the mean ( +/- SEM) percent of entries and time spent in the open arms of young (35 +/- 3 and 20 +/- 4, respectively) and adult (36 +/- 7 and 17 +/- 5, respectively) normotensive Wistar rats. Treatment with magnesium oxide did not alter the performance of SHR in the elevated plus-maze. SHR showed an anxiolytic-like behavior which was neither influenced by age nor by antihypertensive treatment.

Effects of the antihypertensive drugs alpha-methyldopa and hydralazine on the performance of spontaneously hypertensive rats in the elevated plus-maze.

The effects of antihypertensive drugs on the performance of spontaneously hypertensive rats (SHR) in the elevated plus-maze were determined. Male SHR (3 months old) were submitted to long-term treatment (15 days) with alpha-methyldopa (alpha MD, 5 g/l, N = 10) and hydralazine (HYD, 100 mg/l, N = 10) given orally, diluted in water. After the drug treatment, the performance of the rats in the plus-maze was observed for 5 min in a single test and mean arterial pressure (MAP) and heart rate (HR) were then measured. The antihypertensive drugs reduced MAP significantly (mean +/- SEM: CON = 176.2 +/- 5.2, alpha MD = 157.8 +/- 4.6 and HYD = 150 +/- 4.4 mmHg) and only alpha MD increased HR significantly (mean +/- SEM: CON = 391.7 +/- 13.8, alpha MD = 453.3 +/- 14 and HYD = 368.8 +/- 18.9 bpm). The alpha MD group presented a lower total number of entries (mean +/- SEM: CON = 12.7 +/- 0.7, alpha MD = 8.7 +/- 0.9 and HYD = 12 +/- 0.9) and spent less time in the open arms than the CON (N = 10) and HYD groups (mean +/- SEM: CON = 0.69 +/- 0.04, alpha MD = 0.48 +/- 0.07 and HYD = 0.65 +/- 0.06 s). alpha-Methyldopa acts centrally and hydralazine acts peripherally. The behavioral change of SHR treated with alpha-methyldopa suggests that hypertension seems to be related to central nervous dysfunctions that are affected by an antihypertensive drug with central noradrenergic action.