Melatonin decreases cocaine-induced locomotor activity in pinealectomized rats

Objective: Several studies have shown that the time of day regulates the reinforcing effects of cocaine. Additionally, melatonin and its MT1 and MT2 receptors have been found to participate in modulation of the reinforcing effects of such addictive drugs as cocaine. Loss of the diurnal variation in cocaine-induced locomotor sensitization and cocaine-induced place preference has been identified in pinealectomized mice. In addition, several studies in rodents have shown that administration of melatonin decreased the reinforcing effects of cocaine. The objective of this study was to evaluate the effect of melatonin on cocaine-induced locomotor activity in pinealectomized rats at different times of day (zeitgeber time [ZT]4, ZT10, ZT16, and ZT22). Methods: Naïve, pinealectomized Wistar rats received cocaine at different times of day. Melatonin was administered 30 min before cocaine; luzindole was administered 15 min prior to melatonin and 45 min before cocaine. After administration of each treatment, locomotor activity for each animal was recorded for a total of 30 min. Pinealectomy was confirmed at the end of the experiment through melatonin quantitation by ELISA. Results: Cocaine-induced locomotor activity varied according to the time of day. Continuous lighting and pinealectomy increased cocaine-induced locomotor activity. Melatonin administration decreased cocaine-induced locomotor activity in naïve and pinealectomized rats at different times of day. Luzindole blocked the melatonin-induced reduction in cocaine-induced locomotor activity in pinealectomized rats. Conclusion: Given its ability to mitigate various reinforcing effects of cocaine, melatonin could be a useful therapy for cocaine abuse.

A review on alcohol: from the central action mechanism to chemical dependency / Uma revisão sobre o álcool: do mecanismo de ação central à dependência química

SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

ResumoIntrodução:o álcool é uma substância psicotrópica depressora do sistema nervoso central (SNC), que promove alteração simultânea de inúmeras vias neuronais, gerando profundo impacto neurológico e traduzindo-se em diversas alterações biológicas e comportamentais.Objetivos:descrever as ações do álcool sobre o SNC, identificando as vias de sinalização modificadas e os efeitos biológicos gerados pelo seu consumo.Métodos:revisão bibliográfica, priorizando trabalhos multilinguísticos publicados nos últimos 15 anos.Resultados:são descritas ação direta do álcool em inúmeros receptores de neurotransmissores (ácido gama-aminobutírico – GABA, glutamato, endocanabinoides AEA e 2-AG, entre outros), ação indireta do álcool no sistema límbico e opioide, ação sobre canais de cálcio, potássio e proteínas reguladas por GABA no hipocampo, além de ações centrais mediadas pela deficiência de vitamina B1.Conclusão:a ação multifocal do álcool sobre o SNC resulta em efeito geral de depressão psicomotora, dificuldades no armazenamento de informações e no raciocínio lógico, incoordenação motora, além da estimulação do sistema de recompensa, o que pode explicar o desenvolvimento da dependência química. O conhecimento das vias de sinalização neuronais alteradas pelo álcool permite reconhecer a descrição de efetores que possam reduzir sua ação central e, assim, vislumbrar novas perspectivas terapêuticas para a reabilitação de adictos a essa substância.

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

Effect of moderate ethanol administration on biochemical indices in streptozotocin-diabetic Wistar rats / Efecto de la administración moderada de etanol sobre los índices bioqumicos en ratas Wistar diabéticas por estreptozotocina

OBJECTIVE: This study was designed to evaluate the effect of moderate ethanol administration on the biochemical indices in streptozotocin (STZ)-diabetic rats. METHODS: Twenty-four male Wistar rats were divided into four groups of six animals each. Groups one and two contained non-diabetic normal rats and normal rats treated with ethanol, respectively. Group three was untreated STZ-diabetic rats and group four was made up of ethanol-treated STZ-diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (35 mg/kg), while ethanol (10%v/v) was given at a dose 2 g/kg thrice per week for three weeks. After the last dose of ethanol and an overnight fasting, rats were sacrificed by cervical dislocation. Blood was collected by syringe from the heart into plain centrifuge tubes. RESULTS: Moderate ethanol administration to STZ-diabetic rats caused a significant (p < 0. 05) increase in relative weight of liver relative to normal. Ethanol intake in STZ-diabetic rats produced an insignificant (p > 0. 05) effect on the levels of fasting blood glucose (FBG) and HbA1c rrelative to the untreated-diabetic group. Moderately, ethanol administration to STZ-diabetic rats produced a marked and significant (p < 0. 05) increase in the levels of serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol and the activities of alanine aminotransferase relative to untreated diabetic rats. Ethanol-treated diabetic rats had significantly (p < 0. 05) lower high-density lipoprotein (HDL)-cholesterol levels, while the activities of lactate dehydrogenase and α-amylase were insignificantly (p > 0. 05) affected. There were no significant (p > 0. 05) differences in all the biochemical indices in normal rats relative to ethanol-treated normal rats. CONCLUSIONS: Moderate ethanol administration did not affect FBG and HbA1c , but altered the lipid profile of STZ-diabetic rats. Moderate ethanol intake may further increase the risk of complications in diabetes.

OBJETIVO: Este estudio se diseñó con el propósito de evaluar el efecto del uso de etanol moderado sobre los índices bioquímicos en ratas Wistar diabéticas por estreptozotocina (STZ). MÉTODOS: Veinticuatro ratas Wistar machos fueron divididas en cuatro grupos de seis animales cada uno. Dos de los grupos tenían ratas normales no diabéticas y ratas normales tratadas con etanol, respectivamente. El tercer grupo estaba formado por ratas diabéticas por STZ no tratadas, y el cuarto por ratas diabéticas por STZ tratadas con etanol. La diabetes fue inducida mediante una inyección intraperitoneal de STZ (35 mg/kg), mientras que el etanol (10% v/v) fue administrado en dosis de 2 g/kg tres veces por semana durante tres semanas. Tras la última dosis de etanol y un ayuno de una noche, las ratas fueron sacrificadas mediante dislocación cervical. La sangre fue recogida del corazón con jeringuillas e introducida en tubos para centrífuga sin graduación. RESULTADOS: La administración moderada de etanol a ratas diabéticas por STZ, causó un aumento significativo (p < 0.05) en el peso relativo del hígado con relación al normal. La ingestión de etanol en ratas diabéticas por STZ tuvo un efecto insignificante (p > 0.05) en los niveles de glucosa en sangre en ayuno (GSA) y HbA1c en relación con grupos diabéticos no tratados. En medida moderada, la administración de etanol a ratas diabéticas por STZ produjo un aumento marcado y significativo (p < 0.05) en los niveles de colesterol total en suero, triglicéridos, el colesterol asociado con las lipoproteínas de baja densidad, o colesterol LDL, y la actividad de la aminotransferasa alanina en relación con las ratas diabéticas no tratadas. Las ratas diabéticas tratadas con etanol tuvieron niveles significativamente disminuidos de colesterol asociado con las lipoproteínas de alta densidad, o colesterol HDL, en tanto que la actividad del lactato deshidrogenasa y la α-amilasa no fue afectada significativamente (p > 0.05). No hubo diferencias significativas (p > 0.05) en todos los índices bioquímicos en las ratas normales con respecto a las ratas normales tratadas con etanol. CONCLUSIONES: El suministro moderado de etanol no afectó el GSA ni el HbA1c , pero alteró el perfil lípido de las ratas diabéticas por STZ. La ingestión moderada de etanol puede aumentar a un más el riesgo de las complicaciones de la diabetes.

Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2 percent for the first week, 5 percent for the second week and 10 percent for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9) or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group). CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

Curso temporal dos efeitos da exposição combinada de nicotina e etanol no sistema colinérgico cerebral durante adolescência / Time course of the effects of combined exposure to nicotine and ethanol in the brain cholinergic system during adolescence

O etanol e a nicotina são as drogas mais comumente usadas no mundo. Como claramente indicado por estudos epidemiológicos, existe uma forte associação entre o tabagismo e o consumo de etanol principalmente durante o período da adolescência. Entretanto, existem poucos estudos em neurobiologia básica que avaliem o efeito da exposição combinada de nicotina e etanol durante o período da adolescência. Considerando que a nicotina é um agonista do receptor colinérgico nicotínico (nAChR) e que tem sido demonstrado que o etanol interage com os nAChRs, o presente trabalho tem como foco o estudo dos efeitos da exposição à nicotina e/ou ao etanol no sistema colinérgico durante a adolescência. Do 30º ao 45º dia pós-natal (PN) camundongos da cepa C57BL/6 foram expostos à nicotina (NIC) e/ou etanol (ETOH). Quatro grupos foram analisados: 1) exposição concomitante (NIC+ETOH) à solução de nicotina (50ug/ml) e etanol (25%, 2g/kg i.p. em dias alternados), 2) exposição a NIC, 3) exposição ao ETOH, 4) exposição ao veículo. Foram quantificadas a expressão/afinidade do [3H] hemicolinium-3 (HC-3) ao transportador de alta afinidade présinaptico de colina, ao final da exposição (PN45), após curto (PN50) e longo período de retirada (PN75). Ao final da exposição, o grupo NIC+ETOH apresentou upregulation de nAChRs, refletindo simples somação dos efeitos da NIC e ETOH no córtex cerebral e sinergismo no mesencéfalo. A upregulation devido à exposição combinada foi mantida mesmo após alguns dias de retirada das drogas. Um mês após o término da exposição, os valores foram semelhantes aos obtidos para os animais veículo. Em PN45, machos NIC apresentaram aumento da ChAT no córtex cerebral, mas o ETOH foi capaz de reverter este efeito. Ao contrário, fêmeas NIC apresentaram diminuição da ChAT. No mesencéfalo, somente ETOH promoveu aumento da ChAT. Já em PN50, o grupo NIC apresentou aumento na ChAT que foi revertido na retirada combinada de NIC+ETOH. Em PN75, o grupo NIC+ETOH...

Nicotine and ethanol are the most commonly consumed drugs. As clearly indicated by epidemiological studies, there is a close interrelationship between smoking and alcohol consumption manly during adolescence period. However, there are few studies on the basic neurobiology of the effects of the combined nicotine and ethanol exposure in the adolescent brain. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChR), the current proposal will focus on the cholinergic effects of nicotine and/or ethanol treatment during adolescence. From the 30th to the 45th postnatal day (PN), C57BL/6 mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: 1) concomitant (NIC+ETOH) exposure of nicotine (50 ug/ml) and ethanol (25%, 2 g/kg i.p. every other day); 2) NIC exposure; 3) ETOH exposure; 4) vehicle. We assessed nAChR (alfa4beta2) binding, choline acetyltransferase (ChAT) activity and [3H] hemicholinium-3 (HC-3) binding to the high affinity presynaptic choline transporter at the end of exposure period (PN45), at short (PN50) and long term (PN75) withdrawal. At the end of exposure period, NIC+ETOH elicited a pronounced upregulation which reflect simple additivity of the effects of nicotine and ethanol in the cerebral cortex and synergism in the midbrain. On PN45, male NIC mice presented an increase in ChAT in the cerebral cortex. However, ETOH reversed this effect. In contrast, female NIC mice presented decreased ChAT activity. In the midbrain, ETOH increased ChAT. On PN50, NIC mice presented an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH long term withdrawal elicited a decrease in ChAT activity. Regarding HC-3, binding was not affected on PN45. ETOH and NIC+ETOH withdrawal promoted a decrease at short and long-term withdrawal. These results provide experimental evidences that nicotine and ethanol during adolescence...

Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids

OBJECTIVE: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. METHOD: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. RESULTS: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of...

OBJETIVO: O objetivo do presente estudo foi o de investigar o efeito da epipregnanolona sobre a influência de neuroesteróides no desenvolvimento da tolerância rápida aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol. MÉTODO: Experimento 1: no Dia 1, grupos de camundongos foram pré-tratados com salina ou com epipregnanolona. Após 30 min, cada grupo foi subdividido recebendo etanol ou salina. Aos 30, 60 e 90 min após as injeções, os animais foram testados no rota-rod ou a temperatura corporal foi avaliada. No Dia 2, todos os grupos receberam etanol e um procedimento similar foi seguido para avaliar a tolerância rápida. O pré-tratamento com a epipregnanolona (0,10-0,30 mg/kg) bloqueou significantemente o desenvolvimento da tolerância aos efeitos de incoordenação motora e hipotermia induzidos pelo etanol em camundongos. Experimento 2 e 3: no Dia 1, grupos de animais foram tratados com epipregnanolona e, após 15 min, cada grupo foi dividido em três grupos para receber sulfato de pregnanolona, sulfato de dehidroepiandrosterona ou salina. Após 30 min, cada grupo foi dividido em dois subgrupos para receber etanol ou salina, respectivamente, e após 30, 60 e 90 min os animais foram testados como no experimento 1. No Dia 2, todos os grupos receberam etanol e 30 min após foram testados como mencionado no experimento 1. RESULTADOS: Considerando a tolerância ao prejuízo motor induzido pelo etanol, a epipregnanolona (0,15 mg/kg) bloqueou a ação estimulatória do sulfato de dehidroepiandrosterona (0,15 mg/kg), mas não afetou a ação do sulfato de pregnanolona (0,08 mg/kg). Entretanto, a epipregnanolona bloqueou a ação inibitória da alotetrahidrodeoxicorticosterona (0,10 mg/kg). Em relação à hipotermia induzida pelo etanol, os resultados demonstraram que o pré-tratamento com epipregnanolona (0,30 mg/kg) bloqueou significantemente a ação estimulatória do sulfato de dehidroepiandrosterona e do sulfato de pregnanolona, bem como a ação...

Pharmacological evaluation of Pachyrrhizus erosus (L) seeds for central nervous system depressant activity.

The research work deals with the screening of ethanol and chloroform extracts of Pachyrrhizus erosus seeds for central nervous system (CNS) depressant activity. The Pachyrrhizus erosus seed is known to contain rotinoids, flavonoids and phenylfuranocoumarin derivatives as chemical components and is reported to have antifungal, antisecretory, insecticides, antibacterial and spasmolytic activity. Since seeds of Pachyrrhizus erosus is used as folk medicine in treatment of insomnia, we made an attempt to study its CNS depressant effect. The different activities studied were potentiation of pentobarbitone-induced sleep, test for locomotor activity, effect on muscle co-ordination, antiaggressive and antianxiety activities. The result of the study reflected that ethanol extract of the seeds (150 mg/kg, p.o) decreased locomotor activity, produced muscle relaxation and showed antianxiety and antiaggressive activity.

Psychopharmacological profile of hydro-alcoholic extract of Euphorbia neriifolia leaves in mice and rats.

The leaf extract of E. neriifolia significantly reduced apomorphine-induced stereotypy in mice at all doses (100, 200, 400 mg/kg body weight) in mice and rats and was devoid of catalepsic effect thereby, suggesting specific dopaminergic receptor modulating activity. The extract (400 mg/kg) potentiated pentobarbitone-induced hypnosis. It showed protection against maximal electro-shock-induced convulsion at 400 mg/kg. E. neriifolia leaf extract had anxiolytic action at 400 mg/kg by increasing the percentage of time spent in open arm in elevated plus-maze. The extract did not reverse scopolamine-induced amnesia on elevated plus-maze. It increased transfer latency at 200 and 400 mg/kg and also in combination with scopolamine. These results indicated anti-anxiety, anti-psychotic and anti-convulsant activity of E. neriifolia leaf extract in mice and rats. Phytochemical study showed the presence of steroidal saponin, reducing sugar, tannins, flavonoids in the crude leaf extract

Effects of chronic ethanol treatment on monoamine levels in rat hippocampus and striatum

We studied the effects of ethanol on concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5-HT) and their metabolites in rat hippocampus and striatum. Ethanol (2 or 4 g/kg, po, from a 20 percent aqueous solution) was administered daily to male Wistar rats (4-13 per group) for 30 days and animals were sacrificed 30 min or 48 h after the last administration. Monoamines were measured by HPLC and considered significant at P < 0.05. A 47 percent increase in 5-HT levels was observed in the hippocampus with 4 g/kg ethanol in the 30-min protocol. Ethanol (2 and 4 g/kg) decreased DA (2114.5 ± 126.4 and 1785.1 ± 234.2 ng/g wet tissue, respectively) and 3,4-dihydroxyphenylacetic acid (DOPAC, 1477.6 ± 132.1 and 1218.8 ± 271.7 ng/g wet tissue, respectively) levels, while the higher dose also decreased NE (159.8 ± 13.5), 5-HT (228.0 ± 46.8) and 5-hydroxy-3-indoleacetic acid (5-HIAA, 304.4 ± 37.2 ng/g wet tissue), in the striatum after a 48-h withdrawal as compared to controls (DA: 3063.9 ± 321.3; DOPAC: 2379.6 ± 256.0; NE: 292.8 ± 50.2; 5-HT: 412.4 ± 36.2; 5-HIAA: 703.9 ± 61.4 ng/g wet tissue). In the 30-min protocol, ethanol (2 or 4 g/kg) decreased striatal NE (66 and 70 percent) and DA (50 and 36 percent) levels. On the other hand, increases were seen in 5-HIAA (146 and 153 percent) and 5-HT (59 and 86 percent) levels. Ethanol (2 g/kg, po) increased the homovanillic acid (HVA)/DA ratio (129 percent) in the striatum in the 30-min protocol, while at the higher dose it increased the HVA/DA ratio in the 48-h protocol (61 percent). These results indicate alterations in monoamines, mainly in the striatum, after chronic ethanol, which are influenced by dose and by the length of time after the last drug administration.

An experimental study of tolerance among alcohol dependent individuals.

BACKGROUND & OBJECTIVES: Continued alcohol use leads to tolerance, however, some dependent individuals lose tolerance despite continued alcohol consumption. The exact mechanism for this is not known. This study evaluated tolerance in alcohol dependent patients in a treatment centre using multiple measures. METHODS: Male patients with alcohol dependence (DSM III R criteria) were chosen and detoxified in an inpatient setting. On day 14 of detoxification, each subject was given ethanol (0.75 g/kg body wt) mixed in an equal amount of placebo (cola) drink once and an equivalent amount of placebo (cola) during the other occasion in a single blind, randomised, cross over manner. Assessment of each subject was made using multiple measures (clinical, neuro-psychological tests, scales for subjective effect and blood alcohol levels), 30 min after intake of each drink. RESULTS: The subjects (n = 26) did not very under the two conditions (alcohol/placebo) as regards subjective effects, tests on logical memory and Bender Gestalt test (BGT). Cognitive screening scores though different under the two conditions, were within the normative range. Of these 26 subjects, 50 per cent showed clinical signs of intoxication after consumption of alcohol. These two groups (impaired vs unimpaired) were comparable on all base-line clinical parameters, assessment of euphoria and sedation, and various neuropsychological tests except BGT under the two conditions (placebo/alcohol). The non-tolerant (impaired) group scored significantly (P < 0.05) worse on BGT after alcohol consumption. INTERPRETATION & CONCLUSIONS: The study suggests that clinical tests were more sensitive in detecting intoxication. Further studies are needed to understand the mechanism of loss of tolerance.

Evaluation of comparative and combined depressive effect of Brahmi, Shankhpushpi and Jatamansi in mice.

Evaluation of depressive activity of drug extract of Brahmi, Jatamansi & Shankhpushpi and their combined effects were studied on 66 mice of either sex. It was found that combined effect of Jatamansi, Shankhpushpi & Brahmi showed the potent depressiveness in mice. While in individual drug extract, jatamansi exhibited more potent effect than other two drugs.

Experimental anxiety and the reinforcing effects of ethanol in rats

In order to examine the relationship between anxiety and reinforcing effects of alcohol, drug-naive male Wistar rats weighing 250-300 g were classified as "anxious" and "non-anxious" in the elevated plus-maze test. A conditioned place preference test was then used to investigate the reinforcing effects of ethanol (EtOH) on these animals. On 2 alternate days, groups of "anxious", "non-anxious" and "normal" rats received intraperitoneal (ip) injections of EtOH (0.5, 1.0 or 1.5 g/kg) immediately before a 15-min confinement to the white compartment. On the 2 intervening days the same rats received ip injections of saline before confinement to the opposite compartment. On day 5, a 15-min free-choice test was carried out with no injections. Rats classified as "anxious" showed a significant, though not dose-dependent preference for all doses of ethanol compared to saline-treated animals. These data demonstrate that rats regarded as "anxious" are more sensitive to the reinforcing effects of EtOH than "non-anxious" and "normal" Wistar rats and emphasize the relevance of the basal levels of anxiety of rats when trying to detect the reinforcing effects of EtOH.

Central nervous system depressant activities of melatonin in rats and mice.

Melatonin (10 and 20 mg/kg) potentiated pentobarbitone (45 mg/kg) induced hypnosis; it (50 and 100 mg/kg) decreased both total and ambulatory activity; produced (10, 25 and 50 mg/kg) hypothermia and possessed (10-400 mg/kg) significant analgesic property both in tail-flick and acetic acid-induced writhing tests. Melatonin in low dose (10 mg/kg) significantly reduced the forced-swimming induced immobility period per se and also reserpine induced immobility. While the antinociceptive effect of melatonin was sensitive to reversal by naloxone (2 mg/kg), other CNS depressant profile resembled the effects of benzodiazepines.

Effect of leaf extract from Clerodendron colebrookianum on CNS function in mice.

Effect of acute multiple (20, 40 and 80 mg/kg body wt, i.p.) doses of C. colebrookianum leaf extract on behaviour, convulsion, analgesia and sedative-hypnosis was studied in mice. A marginal reduction of awareness and motor activity was observed in low (20 mg) and moderate (40 mg) dose level of extract. However, 80 mg dose caused marked inhibition of awareness and motor activity. Grip strength and stereotypy was observed in all the dose levels. The extract alone did not show loss of righting reflex but it prolonged the effect of meprobamate, diazepam, chlorpromazine and pentobarbitone significantly in a dose dependent manner. The extract neither produced analgesia alone nor it altered analgesic effect of morphine and pethidine. Pretreatment of the extract caused significant protection of strychnine and leptazol induced convulsion and mortality. The results suggest a mild (or dose dependent) CNS depressant action of leaf extract of C. colebrookianum in mice.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12- 1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.

Effect of pre-treatment of some calcium channel blockers on catalepsy and stereotypic behaviour in rats.

Effect of pretreatment of intraperitoneally administered Ca-channel blockers Nifedipine (5, 10, 20 mg/kg). Verapamil (5, 10, 20 mg/kg) and Diltiazem (5, 10, 20 mg/kg) was studied on Haloperidol-induced catalepsy and Methamphetamine-induced stereotypy in albino rats. All these drugs reduced the onset of catalepsy, significantly increased the cataleptic score and delayed the onset and inhibited the Methamphetamine-induced stereotypy. The possible involvement of dopaminergic and adrenergic mechanisms and modification by Ca-channel blockers are discussed.

Cyclodiene insecticides-induced changes in the central depressive effect of chlorpromazine in rats.

Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle coordination (MC) and pentobarbital sleep were tested in rats treated orally for 90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened pentobarbital sleeping time indicating their microsomal enzyme inducing property. Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited CAR and unaltered MC. However, their concurrent action with CPZ did not result in change in the central depressive effects of the latter, but its potency during the course of its action was altered. Its potency 15 min after injection was greater and 60-180 min later was lesser in these animals than that observed in control animals. This finding was interpreted to suggest that aldrin and endosulfan has quickened the biotransformation of CPZ and thereby shortened its duration of action. A temporary promotion of its potency was accounted to its active metabolites, since prior to inactivation, CPZ is known to be metabolized by the microsomal enzymes to active compounds.

Atividade depressora do sistema nervoso central da iangambina / Depressant activity of central nervous system of iangambina

Neste estudo, os autores relatam os dados da avaliaçao dos efeitos a nível do sistema nervoso central da iangambina, uma lignana furofurânica isolada da Ocotea duckei Vattimo. Os principais efeitos observados em camundongos, foram: potencializaçao do tempo de sono induzido por pentobarbital e bloqueio das convulsoes induzidas por pentilenotetrazol.

Agentes antiinflamatórios näo-hormonais e a funçäo labiríntica / Anti-inflamatory agents non-hormone and the function labirints

O uso do nimesulide näo provocou a ocorrência de sintomas e sinais de disfunçäo vestibular em pacientes com doenças reumáticas, ao contrário do que se verificou com o uso de diclofenaco sódico, naproxeno sódico e ibuprofeno; a diferença entre diclofenaco e nimesulide, quanto à ocorrência de sintomas e sinais vestibulares neste grupo de pacientes, foi estatisticamente significante