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M A Benedito

Publications and source records attributed to M A Benedito.

At least 19 recordsLinked to original sources
PubMed2001

Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions.

Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei) are involved in the generation of rapid eye movement (REM) sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase), the enzyme which inactivates acetylcholine (Ach) in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase) are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex) after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min(-1) mg protein(-1)) were assayed photometrically. The results (mean +/- SD) obtained showed a statistically significant (Student t-test) increase in total Achase activity in the pons (control: 147.8 +/- 12.8, REM sleep-deprived: 169.3 +/- 17.4, N = 6 for both groups, P<0.025) and thalamus (control: 167.4 +/- 29.0, REM sleep-deprived: 191.9 +/- 15.4, N = 6 for both groups, P<0.05). Increases in membrane-bound Achase activity in the pons (control: 171.0 +/- 14.7, REM sleep-deprived: 189.5 +/- 19.5, N = 6 for both groups, P<0.05) and soluble enzyme activity in the medulla oblongata (control: 147.6 +/- 16.3, REM sleep-deprived: 163.8 +/- 8.3, N = 6 for both groups, P<0.05) were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity induced by REM sleep deprivation was specific to the pons, a brain region where cholinergic neurons involved in REM generation are located, and also to brain regions which receive cholinergic input from the pons (the thalamus and medulla oblongata). During REM sleep extracellular levels of Ach are higher in the pons, medulla oblongata and thalamus. The increase in Achase activity in these brain areas after REM sleep deprivation suggests a higher rate of Ach turnover.

Acetylcholinesterase↗
PubMed1999

Sex-dependent differences in the activities of acetylsalicylic acid-esterases in mouse kidneys.

Acetylsalicylic acid (ASA), the most used drug worldwide, is hydrolyzed to salicylic acid and acetate by esterases present in tissues of several species including humans. Sex differences in drug metabolism by rodent liver are documented in the literature. In this paper we report a difference in the activities of the esterases (ASA-esterase I and II) in the kidneys of male and female mice. In this species there is no difference between males and females in liver ASA-esterases (ASA-esterase I: males 38.5 +/- 7.9 (N = 5) and females 31.6 +/- 7.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P > 0.05; ASA-esterase II: males 77.3 +/- 17.4 (N = 5) and females 61.4 +/- 15.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P > 0.05). However, in the kidneys males presented a much higher enzyme activity than females (ASA-esterase I: males 25.2 +/- 6.3 (N = 5) and females 6.8 +/- 0.6 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P < 0.0002; ASA-esterase II: males 79.8 +/- 10.1 (N = 5) and females 13.0 +/- 1.1 (N = 5) nmol of salicylic acid formed min-1 mg protein-1, P < 0.0001). The difference between sexes observed in mouse kidneys could serve as a model to study the molecular basis of this sex difference and also to determine the possible involvement of pituitary and gonadal hormones in this difference in ASA-esterase activities since these hormones control the sex differences in rodent liver enzyme activity.

Animals↗
PubMed1998

Decreased activity of striatal monoamine oxidase B after rapid eye movement (REM) sleep deprivation in rats.

The striatum seems to be the main brain region involved in stereotyped behavior induced by dopaminergic agonists. Rapid eye movement (REM) sleep deprivation increases dopaminergic agonist-induced stereotypy and produces biochemical changes in striatal dopaminergic neurotransmission. However, the mechanism underlying the increased dopaminergic sensitivity induced by REM sleep deprivation has not been elucidated. In an attempt to determine some of the biochemical changes in striatal dopaminergic neurotransmission that could contribute to REM sleep deprivation effects, we measured the activity of monoamine oxidase (MAO) A and B, the enzymes responsible for dopamine and beta-phenylethylamine (beta-PEA) deamination in striatum. Male adult rats were deprived of REM sleep for 96 h by the flower-pot technique. MAO A and B were assayed radioisotopically in the mitochondrial fraction by standard laboratory procedures, using [14C]-5-hydroxytryptamine (5-HT) and [14C]-beta-phenylethylamine (beta-PEA), as substrates for MAO A and MAO B, respectively. The results showed no significant statistical differences in striatal MAO A activity, whereas a significant decrease in MAO B activity was observed. The results are discussed in terms of the possible involvement of beta-PEA, a striatal endogenous trace amine, which potentiates dopaminergic neurotransmission and may participate in the increased dopaminergic sensitivity observed after REM sleep deprivation.

Animals↗
PubMed1998

Gender differences in the activities of aspirin-esterases in rat tissues.

The activities of aspirin (acetylsalicylic acid)-esterases were measured in several tissues (liver, kidney, adrenal glands, brain and serum) from adult male and female Wistar rats. In males, both aspirin-esterase I (assayed at pH 5.5) and II (assayed at pH 7.4) activities were higher in liver homogenates when compared to females (aspirin-esterase I: males 48.9 +/- 4.8 (N = 8) and females 29.3 +/- 4.2 (N = 8) nmol of salicylic acid formed min-1 mg protein-1; aspirin-esterase II: males 41.4 +/- 4.1 (N = 8) and females 26.1 +/- 4.5 (N = 8) nmol of salicylic acid formed min-1 mg protein-1, P < 0.001). In serum, enzyme activity was higher in females than in males (aspirin-esterase I: males 0.85 +/- 0.06 (N = 6) and females 1.18 +/- 0.11 (N = 6) nmol of salicylic acid formed min-1 mg protein-1, aspirin-esterase II: males 1.03 +/- 0.13 (N = 6) and females 1.34 +/- 0.11 (N = 6) nmol of salicylic acid formed min-1 mg protein-1, P < 0.001). In the other tissues assayed, no statistically significant difference between males and females was found. There were no statistically significant differences when the enzymes were assayed in different phases of the estrous cycle in liver and serum. These results show that the differences in aspirin-esterase activity observed between males and females are not due to the estrous cycle. The gender difference obtained in our study may indicate an involvement of gonadal hormones in the control of the hydrolysis of aspirin. This possibility is currently under investigation.

Adrenal Glands↗
PubMed1997

Activities of monoamine oxidase (MAO) A and B in discrete regions of rat brain after rapid eye movement (REM) sleep deprivation.

Rapid eye movement (REM) sleep deprivation increases monoaminergic (noradrenergic and serotonergic) turnover and their metabolites in whole brain of rats. This increase in metabolites may indicate increased activity of the enzymes responsible for the inactivation of monoamines. To test this hypothesis, we assayed the activity of monoamineoxidases (MAOs) A and B in hippocampus, hypothalamus, brainstem and its divisions pons and medulla oblongata in rats deprived of REM sleep for 96 h. REM sleep deprivation was carried out by the flower-pot technique. A control group remained in their home cages. MAO A was assayed by using [14C]-5-hydroxytryptamine as the substrate (50 microM final concentration) and MAO B by using [14C]-beta-phenylethylamine (2 microM final concentration). The enzymes were assayed in the mitochondrial fraction.The results obtained showed that a significant decrease in the activity of MAO A was obtained in the brainstem and an increase in medulla oblongata and no statistical differences in the activity of MAO B in brainstem, pons and medulla oblongata and MAO A in pons; there were also no differences in the activities of both MAO A and B in hippocampus and hypothalamus. Although our results confirmed previous data regarding changes in MAO A activity in brainstem and medulla oblongata, they did not confirm our hypothesis that the increase in monamine turnover and metabolites in the brain would be the result of increased MAO activity.

Animals↗
PubMed1997

Fluorimetric determination of tissue distribution and differences between the activity of aspirin esterases I and II in mice and rats.

A modification of available fluorimetric methods, based on the native fluorescence of salicylic acid, has been used to assay the activity of aspirin esterases I and II in small amounts of several tissues from rats and mice. The results obtained showed that aspirin esterase I from mouse liver and kidney had the lowest activity and that the activity of aspirin esterase II from these organs was greater than that from the same organs from rats. Liver enzyme kinetics and tissue distribution in rats was shown to be similar to previous data obtained using a spectrophotometric method. This fluorimetric method, which is more sensitive and rapid than the spectrophotometric method, may be useful in studies on aspirin metabolism.

Adrenal Glands↗
PubMed1997

Rapid eye movement (REM) sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7) activity.

Rapid eye movement (REM) sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase) controls acetylcholine (Ach) availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12). Two additional groups, a home-cage control (N = 6) and a large platform control (N = 6), were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant), membrane-bound (100,000 g pellet) and soluble (100,000 g supernatant) Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet) enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) in the 100,000 g pellet enzyme preparation (home-cage group 152.1 +/- 5.7, large platform group 152.7 +/- 24.9 and REM sleep-deprived group 127.9 +/- 13.8). There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 +/- 21.5, large platform group 127.8 +/- 20.4, REM sleep-deprived group 102.8 +/- 14.2). Our results suggest that REM sleep deprivation changes Ach availability at the level of its receptors through a decrease in Achase activity.

Acetylcholine↗
PubMed1997

Chronic imipramine treatment-induced changes in acetylcholinesterase (EC 3.1.1.7) activity in discrete rat brain regions.

Cholinergic as well as monoaminergic neurotransmission seems to be involved in the etiology of affective disorders. Chronic treatment with imipramine, a classical antidepressant drug, induces adaptive changes in monoaminergic neurotransmission. In order to identify possible changes in cholinergic neurotransmission we measured total, membrane-bound and soluble acetylcholinesterase (Achase) activity in several rat brain regions after chronic imipramine treatment. Changes in Achase activity would indicate alterations in acetylcholine (Ach) availability to bind to its receptors in the synaptic cleft. Male rats were treated with imipramine (20 mg/kg, i.p.) for 21 days, once a day. Twenty-four hours after the last dose the rats were sacrificed and homogenates from several brain regions were prepared. Membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) after chronic imipramine treatment was significantly decreased in the hippocampus (control = 188.8 +/- 19.4, imipramine = 154.4 +/- 7.5, P < 0.005) and striatum (control = 850.9 +/- 59.6, imipramine = 742.5 +/- 34.7, P < 0.005). A small increase in total Achase activity was observed in the medulla oblongata and pons. No changes in enzyme activity were detected in the thalamus or total cerebral cortex. Since the levels of Achase seem to be enhanced through the interaction between Ach and its receptors, a decrease in Achase activity may indicate decreased Ach release by the nerve endings. Therefore, our data indicate that cholinergic neurotransmission is decreased after chronic imipramine treatment which is consistent with the idea of an interaction between monoaminergic and cholinergic neurotransmission in the antidepressant effect of imipramine.

Acetylcholinesterase↗
PubMed1997

Acetylcholinesterase activity in the pons and medulla oblongata of rats after chronic electroconvulsive shock.

An imbalance between cholinergic and noradrenergic neurotransmission has been proposed for the etiology of affective disorders. According to this hypothesis, depression would be the result of enhanced cholinergic and reduced noradrenergic neurotransmission. Repeated electroconvulsive shock (ECS) is an effective treatment for depression; moreover, in laboratory animals it induces changes in brain noradrenergic neurotransmission similar to those obtained by chronic treatment with antidepressant drugs (down-regulation of beta-adrenergic receptors). The aim of the present study was to determine whether repeated ECS in rats changes acetylcholinesterase (Achase) activity. Achase controls the level of acetylcholine (Ach) in the synaptic cleft and its levels seem to be regulated by the interaction between Ach and its receptor. Thus, a decrease in Achase activity would suggest decreased cholinergic activity. Adult male Wistar rats received one ECS (80 mA, 0.2 s, 60 Hz) daily for 7 days. Control rats were handled in the same way without receiving the shock. Rats were sacrificed 24 h after the last ECS and membrane-bound and soluble Achase activity was assayed in homogenates obtained from the pons and medulla oblongata. A statistically significant decrease in membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1) (control 182.6 +/- 14.8, ECS 162.2 +/- 14.2, P < 0.05) and an increase in soluble Achase activity in the medulla oblongata (control 133.6 +/- 4.2, ECS 145.8 +/- 12.3, P < 0.05) were observed. No statistical differences were observed in Achase activity in the pons. Although repeated ECS induced a decrease in membrane-bound Achase activity, the lack of changes in the pons (control Achase activity: total 231.0 +/- 34.5, membrane-bound 298.9 +/- 18.5, soluble 203.9 +/- 30.9), the region where the locus coeruleus, the main noradrenergic nucleus, is located, does not seem to favor the existence of an interaction between cholinergic and noradrenergic neurotransmission after ECS treatment.

Acetylcholinesterase↗
PubMed1990

Daily changes in pentylenetetrazol-induced convulsions and open-field behavior in rats.

Susceptibility to pentylenetetrazol (PTZ)-induced clonic convulsions was measured in rats over the 24-hr light-dark cycle at four-hour intervals. The results showed a higher sensitivity to PTZ around 2200 hr. Other groups of rats were exposed to a four-min open-field session. In the first two min of the session the animals were submitted to open-field environmental stimuli. The next two-min observation occurred with sound and light presented to the animals. Differences through the 24-hr period of the day for both sessions were seen. A reduction in rearing at 2200 hr and increase in defecation at 2200 hr and 0200 hr was observed.

Animals↗
PubMed1986

REM sleep deprivation induces a decrease in norepinephrine-stimulated 3H-cyclic AMP accumulation in slices from rat brain.

Beta adrenergic sites in rat brain are reduced after repeated treatment with antidepressant drugs, with REM sleep deprivation (REMSd) having the same effect. This paper reports the effects of REMSd in the production of 3H-cyclic AMP in frontal cortical slices by NE challenge. Data presented in this paper report a marked decrease in 3H-cyclic AMP synthesis after REMSd, which is in accordance with previous results showing adrenergic receptor down-regulation following REMSd. Results are discussed in view of possible interaction with dopaminergic systems and depression management.

Adenylyl Cyclases↗
PubMed1986

Circadian rhythms in neurotransmitter receptors in discrete rat brain regions.

Circadian rhythms were measured in alpha 1-, alpha 2- and beta-adrenergic, acetylcholine muscarinic (ACh), and benzodiazepine (BDZ) receptor binding in small regions of rat brain. Rhythms in alpha 1-receptor binding were measured in olfactory bulb, frontal, cingulate, piriform, parietal, temporal and occipital cortex, hypothalamus, hippocampus, pons-medulla, caudate-putamen and thalamus-septum. No rhythm was found in cerebellum. Rhythms in alpha 2-receptor binding were measured in frontal, parietal and temporal cortex, and pons-medulla. No rhythm was found in cingulate, piriform or occipital cortex, or hypothalamus. Rhythms in binding to beta-receptors were measured in olfactory bulb, piriform, insular, parietal and temporal cortex, hypothalamus and cerebellum. No rhythms were found in frontal, entorhinal, cingulate, or occipital cortex, hippocampus, caudate-putamen, or pons-medulla. Rhythms in ACh receptor binding were measured in olfactory bulb, parietal cortex and caudate-putamen. No rhythms were found in frontal or occipital cortex, nucleus accumbens, hippocampus, thalamus-septum, pons-medulla or cerebellum. Rhythms in BDZ receptor binding were measured in olfactory bulb, olfactory and occipital cortex, olfactory tubercle, nucleus accumbens, amygdala, caudate-putamen, hippocampus and cerebellum. No rhythms were found in parietal cortex, pons-medulla or thalamus-septum. The 24-hr mean binding to receptors varied between 3- and 10-fold, the highest in cortex and the lowest, usually, in cerebellum. The piriform cortex was particularly high in alpha 1- and alpha 2-adrenergic receptors; the nucleus accumbens and caudate, in ACh receptors; and the amygdala, in BDZ receptors. Most adrenergic and ACh receptor rhythms peaked in subjective night (the period when lights were off under L:D conditions), whereas most BDZ receptor rhythms peaked in subjective day (the time lights were on in L:D). Perhaps in the rat, a nocturnal animal, the adrenergic and ACh receptors mediate activity and the functions that accompany it, and the BDZ receptors mediate rest, and with it, sleep.

Animals↗
PubMed1986

Circadian rhythms in catecholamine metabolites and cyclic nucleotide production.

Circadian rhythms in noradrenergic (NE) and dopaminergic (DA) metabolites and in cyclic nucleotide production were measured in discrete regions of rat brain. A circadian rhythm was found in the concentration of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in the hippocampus. No MHPG rhythm was found in frontal, cingulate, parietal, piriform, insular or temporal cortex, or in hypothalamus. Circadian rhythms in the concentration of the NE metabolite, 3,4-dihydroxyphenylglycol (DHPG), occurred in occipital and parietal cortex and hypothalamus, with no rhythm observable in temporal or insular cortex, hippocampus, pons-medulla or cerebellum. The 24-hr mean concentration of MHPG varied 3.5-fold, highest in cingulate and lowest in parietal, temporal and occipital cortex. The 24-hr mean concentration of DHPG varied 6-fold, highest in hypothalamus and lowest in parietal cortex. Circadian rhythms in the concentration of the DA metabolite, homovanillic acid (HVA), were found in olfactory tubercle, amygdala and caudate-putamen, but not in nucleus accumbens. A circadian rhythm in the concentration of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), occurred in nucleus accumbens, but not in olfactory tubercle or caudate-putamen. The mean 24-hr concentration of HVA was highest in caudate-putamen, intermediate in nucleus accumbens, and lowest in olfactory tubercle and amygdala. The mean 24-hr concentration of DOPAC was highest in nucleus accumbens and lower in olfactory tubercle and caudate-putamen. Circadian rhythms were found in the concentration of cyclic GMP (cGMP) in all regions measured except parietal cortex. The mean 24-hr concentration varied 128-fold, highest in nucleus accumbens, frontal poles, and hypothalamus and lowest in cingulate cortex. Circadian rhythms in cyclic AMP (cAMP) concentration were found in piriform, temporal, occipital, cingulate, and parietal cortex, amygdala and nucleus accumbens. No rhythms were found in frontal or insular cortex, hypothalamus, hippocampus, caudate-putamen or olfactory tubercle. The 24-hr mean cAMP concentration varied 4-fold, highest in parietal cortex and lowest in caudate-putamen and amygdala. Norepinephrine metabolites and dopamine metabolites were rhythmic in few regions. It is, therefore, unlikely that the rhythmicity measured in adrenergic receptors is, in general, a response to rhythmic changes in adrenergic transmitter release. The putative second messenger response systems, especially cGMP, were more often rhythmic. The rhythms in cGMP are parallel in form and region to those in the alpha 1-adrenergic receptor and may act as 2nd messenger for that receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Relationships between behavioral rhythms, plasma corticosterone and hypothalamic circadian rhythms.

Circadian rhythms in physiological processes and behaviors were compared with hypothalamic circadian rhythms in norepinephrine (NE) metabolites, adrenergic transmitter receptors, cAMP, cGMP and suprachiasmatic nucleus (SCN) arginine vasopressin (AVP) in a single population of rats under D:D conditions. Eating, drinking and locomotor activity were high during the subjective night (the time when lights were out in L:D) and low during the subjective day (the time when lights were on in L:D). Plasma corticosterone concentration rose at subjective dusk and remained high until subjective dawn. Binding to hypothalamic alpha 1- and beta-adrenergic receptors also peaked during the subjective night. Cyclic cGMP concentration was elevated throughout the 24-hr period except for a trough at dusk, whereas DHPG concentration peaked at dawn. Arginine vasopressin levels in the suprachiasmatic nucleus peaked in the middle of the day. No rhythm was found either in binding to the alpha 2-adrenergic receptor, or in MHPG or cAMP concentration. Behavioral and corticosterone rhythms, therefore, are parallel to rhythms in hypothalamic alpha 1- and beta-receptor binding and NE-release. Cyclic GMP falls only at dusk, suggesting the possibility that cGMP inhibits activity much of the day and that at dusk the inhibition of nocturnal activity is removed. SCN AVP, on the other hand, peaking at 1400 hr, may play a role in the pacemaking function of the SCN that drives these other rhythms.

Animals↗
PubMed1983

Circadian rhythms in rat brain neurotransmitter receptors.

In the rat brain there are daily rhythms in the number of alpha- and beta-adrenergic, muscarinic cholinergic, dopamine, opiate, and benzodiazepine receptors. The rhythms are circadian, i.e., with periods of approximately 24 h and endogenously generated. The characteristics of the circadian rhythms change over the year. Ablation of the suprachiasmatic nuclei, believed to act as a biological clock, abolishes the circadian rhythms. In the cerebral cortex the circadian rhythm in norepinephrine-stimulated cyclic AMP production is a biological response to the circadian rhythms in alpha- and beta-adrenergic receptors. The effects on neurotransmitter receptor rhythms of treatments that are antidepressant in humans were studied. Chronic administration of the antidepressant drugs imipramine and clorgyline delays the timing of the peak number of many receptors. Chronic administration of the antidepressant, antimanic drug lithium carbonate delays the timing of the peak number of some receptors and abolishes the rhythms in several others. Twenty-four hours of sleep deprivation is almost without effect on the rhythms. Fluphenazine and lithium, both antimanic in humans, increase the 24-h mean number of most receptors. Circadian receptor rhythms evoking intracellular circadian biological responses may modulate brain neurotransmission, coordinating internal physiological processes, and synchronizing them to environmental events. Alterations in circadian receptor rhythms with chronic psychoactive drug administration may play a role in the therapeutic actions of these drugs.

Animals↗
PubMed1982

Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice.

In mice, running, clonic and tonic convulsions and lethality were assessed following transcorneal (electroshock) current or convulsant drugs, each administered alone and after cannabidiol (CBD) pretreatment. CBD prevented tonic convulsions caused by a convulsant current (CC) 99.99, and by the convulsant dose (CD) 99.99 values of gamma-aminobutyric acid (GABA) inhibitors, 3-mercaptoproprionic acid (3MPA), picrotoxin (PIC), isonicotinic acid hydrazine (INH), pentylenetetrazol (PTZ) and bicuculline (BIC). Rankorder potencies, based on the antitonic ED50 of CBD, were: 3MPA greater than PIC = current = PTZ = BIC. Further, CBD prevented 3MPA-induced lethality, but failed to prevent the occurrence of the other behavioral endpoints of the above treatments. CBD also failed to prevent convulsions and lethality caused by the CD 99.99 of strychnine, a glycine antagonist. The differential effects of CBD suggest that the cannabinoid acts to inhibit seizure spread in the CNS by an action on GABA, but not glycine, mechanisms.

Animals↗