Ellagic acid enhances the antinociceptive action of carbamazepine in the acetic acid writhing test with mice

Context: Ellagic acid (EA) produced antinociceptive and anti-inflammatory effects through the central and peripheral sites of action.

Objective: The objective of the current study was to examine the functional interaction between ellagic acid and carbamazepine (CBZ) on pain.

Materials and methods: Fourteen groups of mice (8–10 each) were used in this study. Pain was induced by intraperitoneal acetic acid in mice (writhing test) and the functional interaction was analyzed using the isobolographic method. EA at doses 0.3, 1, 3, and 10?mg/kg and carbamazepine at doses 3, 10, 20, and 30?mg/kg, alone and also in combination (1/2, 1/4, and 1/8 of the drug’s ED₅₀) were intraperitoneally administered 30?min before acetic acid (0.6% v/v). Then, the abdominal writhes were counted during a 25-min period.

Results: EA (0.3–10?mg/kg, i.p.) and CBZ (3–30?mg/kg, i.p.) inhibited the writhing response evoked by acetic acid. Fifty percent effective dose (ED₅₀) values against this tonic pain were 1.02?mg/kg and 6.40?mg/kg for EA and CBZ, respectively. The antinociception induced by EA showed higher potency than that of carbamazepine. Co-administration of increasing fractional increments of ED₅₀ values of EA and CBZ produced additive interaction against writhing responses, as revealed by isobolographic analysis.

Discussion and conclusion: These results suggest that a combination of carbamazepine and ellagic acid may be a new strategy for the management of neuropathic pain such as what occurs in trigeminal neuralgia, since the use of carbamazepine is often limited by its adverse effects and by reduction of its analgesic effect through microsomal enzyme induction.     

Antidepressant and anxiolytic activity of Lavandula officinalis aerial parts hydroalcoholic extract in scopolamine-treated rats

Context: Anxiety and depression are common in Alzheimer’s disease (AD). Despite some evidence, it is difficult to confirm Lavandula officinalis Chaix ex Vill (Lamiaceae) as an anxiolytic and antidepressant drug.

Objective: The effects of L. officinalis extract were studied in scopolamine-induced memory impairment, anxiety and depression-like behaviour.

Materials and methods: Male NMRI rats were divided into control, scopolamine alone-treated group received scopolamine (0.1?mg/kg) intraperitoneally (i.p.), daily and 30?min prior to performing behavioural testing on test day, for 12 continuous days and extract pretreated groups received aerial parts hydro alcoholic extract (i.p.) (100, 200 and 400?mg/kg), 30?min before each scopolamine injection. Memory impairment was assessed by Y-maze task, while, elevated plus maze and forced swimming test were used to measure anxiolytic and antidepressive-like activity.

Results: Spontaneous alternation percentage in Y maze is reduced by scopolamine (36.42?±?2.60) (p?≤?0.001), whereas lavender (200 and 400?mg/kg) enhanced it (83.12?±?5.20 and 95?±?11.08, respectively) (p?≤?0.05). Also, lavender pretreatment in 200 and 400?mg/kg enhanced time spent on the open arms (15.4?±?3.37 and 32.1?±?3.46, respectively) (p?≤?0.001). On the contrary, while immobility time was enhanced by scopolamine (296?±?4.70), 100, 200 and 400?mg/kg lavender reduced it (193.88?±?22.42, 73.3?±?8.25 and 35.2?±?4.22, respectively) in a dose-dependent manner (p?≤?0.001).

Discussion and conclusion: Lavender extracts improved scopolamine-induced memory impairment and also reduced anxiety and depression-like behaviour in a dose-dependent manner.     

Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for protection against scopolamine-induced amnesia

Abstract

Context: Gallic acid (GA) has well-documented antioxidant and CNS effects affecting glutathione, catalase and malonaldehyde levels in brain.

Objective: This study was designed to evaluate the anti-amnesic activity of pure GA in scopolamine (SC)-induced amnesic models and to enhance its effects using Tween 80®-coated nanoparticles.

Methods: GA-loaded chitosan nanoparticles (GANP) and corresponding Tween 80®-coated batch (cGANP) were formulated. Amnesia was induced by using SC (0.4?mg/kg, i.v.). GA, GANP, cGANP (dose equivalent to GA 10?mg/kg, i.p.) and positive control Piracetam (400?mg/kg, i.p.) were administered for successive 7 days to male Swiss albino mice. The in vivo pharmacodynamic study was performed using Morris water maze (MWM) and elevated plus maze (EPM) models; locomotor activity using photoactometer and brain acetyl cholinesterase (AChE) activity was also studied.

Key findings: GA-treated mice exhibited significant decrease in transfer latency in the EPM test; increase in time spent in target quadrant in MWM and reduced AChE activity. GA significantly reversed SC-induced amnesic activity. There was no significant change in locomotor activity of the mice by GA and its nanoparticle formulations. These effects were significantly increased by the administration of cGANP compared with pure GA administration but no significant change was observed for GANP.

Conclusion: GA possesses anti-amnesic activity by reversing the SC-induced amnesia which may be attributed to its anti-cholinesterase activity. Tween 80®-coated nanoparticle approach with improved brain targeting may serve as an effective approach to enhance its anti-amnesic effect.     

Protective effect of Cnestis ferruginea and its active constituent on scopolamine-induced memory impairment in mice: A behavioral and biochemical study

Abstract

Context: Cnestis ferruginea Vahl ex DC (Connaraceae) (CF) is used in traditional African medicine in the management of CNS disorders. The degeneration and dysfunction of cholinergic neurons is closely associated with the cognitive deficits of Alzheimer’s disease (AD) and oxidative stress has been implicated in its pathogenesis. However, the influence of C. ferruginea on the cholinergic system and oxidative stress parameters has not been explored.

Objective: The present study investigates the effect of methanol root extract of C. ferruginea and its active constituent amentoflavone (CF-2) on memory, oxidative stress and acetylcholinesterase (AChE) activity in scopolamine-induced amnesia.

Materials and methods: Mice were orally treated with CF (25–200?mg/kg), CF-2 (6.25–25?mg/kg) for three days and memory impairment was induced by intraperitoneal injection of scopolamine (3?mg/kg). Memory function was evaluated by passive avoidance and Morris water maze tests. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain after the completion of behavioral studies.

Results: Scopolamine caused memory impairment along with increased AChE activity and oxidative stress in mice brain. Oral administration of CF and CF-2 significantly prevented scopolamine-induced memory impairment, inhibited AChE and enhanced antioxidant enzyme activity in the brain following scopolamine injection as compared to vehicle administration in scopolamine (i.p.)-treated mice that were comparable to the effect of tacrine.

Discussion and conclusion: The study demonstrated that C. ferruginea and its constituent have significant protective effect against scopolamine-induced memory deficits in mice that can be attributed to their antioxidant and antiAChE activity.     

Effects of vinpocetine in scopolamine-induced learning and memory impairments

Scopolamine-induced memory dysfunctions are related to reduced cholinergic transmission. In our experiments scopolamine (3.0 mg/kg i.p.) inhibited acquisition and induced retrograde amnesia in a one-trial step- through passive avoidance task in mice. We have studied the effect of vinpocetine (Cavinton^R), in the amnesic states mentioned above compared to that of vincamine, nicergoline (Sermion^R), and papaverine, to assess its activity on learning and memory processes impaired by scopolamine. Vinpocetine decreased the disrupting effect of scopolamine on acquisition and prevented and restituted the memory loss with 21.0 and 7.0 mg/kg i.p. peak effect dose, respectively. It facilitated the recall of memory traces damaged by scopolamine. Vincamine (3.5–63.7 mg/kg i.p.) showed a favorable effect in two of the four tests (reversal of amnesia and recall). Nicergoline (5–40 mg/kg i.p.) exerted moderate activity, and papaverine (10–40 mg/kg i.p.) was ineffective in the situations tested. Our findings indicate that vinpocetine directly or indirectly influences the cholinergic system, which may explain its previously reported beneficial effect in electroconvulsive shock- and hypoxia-induced experimental amnesic states, and its therapeutic activity in human mental and cognitive disorders.     

Pharmacological evaluation of the anxiolytic-like effects of Lippia graveolens and bioactive compounds

Context: Lippia species (Verbenaceae) are widely used in Latin America and Africa as folk medicine for their tranquilizing properties.

Objective: To evaluate the anxiolytic-like effects and safety of Lippia graveolens Kunth. by exploring its aqueous and organic leaf extracts and identifying the responsible chemical constituents.

Material and methods: Aqueous and organic extracts (hexane, ethyl acetate and methanol) were pharmacologically evaluated at several doses. Chemical constituents were identified using MS, NMR and GC-MS analysis. The isolated compounds (3?mg/kg, i.p.), extracts (1, 3, 10 and 30?mg/kg, i.p.), and the reference drug diazepam (0.1?mg/kg, i.p.) were assessed in CD-1 mice using experimental behavioural models: open-field, cylinder, hole-board, plus-maze and sodium pentobarbital-induced hypnosis, as well as their acute toxicity (LD₅₀).

Results: After administration of the extracts and bioactive compounds, a significant anxiolytic-like response from 1?mg/kg, i.p. was observed, resembling the effect of diazepam. Major presence of thymol (33.40%) was observed in the hexane extract; whereas for the first time in this species a p-cymene?+?thymol mixture (9.78%), naringenin (0.18%) and cirsimaritin (1.16%) were obtained as bioactive constituents of the ethyl acetate crude extract. Acute toxicity was calculated to be LD₅₀ =?1000?mg/kg for the crude hexane extract, lower in comparison to the other extracts analyzed (LD₅₀ >?2000?mg/kg).

Discussion and conclusion: Our results suggest that L. graveolens exerts anxiolytic-like activity involving many kinds of constituents, mainly of the terpenoid and flavonoid nature. These results reinforce the potential use of this species in the therapy of anxiety.     

Effect of Anwala churna (Emblica officinalis GAERTN.): an ayurvedic preparation on memory deficit rats

The present study was aimed at investigating the effects of Anwala churna (Emblica officinalis GAERTN.), an Ayurvedic preparation, on memory in rats. Anwala churna was administered orally in three doses (50, 100 and 200 mg/kg) for 15 days to different groups of young and aged rats. The elevated plus-maze and Hebb-Williams maze served as exteroceptive behavioral models for testing memory. Diazepam-, scopolamine-, and ageing induced amnesia served as the interoceptive behavioral models. Anwala churna (50, 100, and 200 mg/kg, p.o.) produced a dose-dependent improvement in memory scores of young and aged rats. Furthermore, it reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Based on these results, Anwala churna may prove to be a useful remedy for the management of Alzheimer's disease due to its multifarious beneficial effects such as memory improvement and reversal of memory deficits.     

Evaluation of the Anticonvulsant and Anxiolytic Potentials of Methyl Jasmonate in Mice

Methyl jasmonate (MJ) is one of the most well-studied plant stress hormones belonging to the jasmonate family. Previous studies have shown that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting potential benefits in disorders associated with hyperactivity of the brain. This study was carried out to evaluate whether MJ has anticonvulsant and anxiolytic properties in mice. The anticonvulsant effect was assessed based on the prevention of tonic-clonic seizures induced by chemoconvulsant agents in mice. The anxiolytic property was evaluated utilizing the elevated plus maze (EPM) and light/dark transition paradigms. The effect of MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received intraperitoneal (i.p.) injections of MJ 30 min before the tests were carried out and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50–400 mg/kg) did not protect the mice against tonic-clonic convulsions induced by picrotoxin (10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200, and 400 mg/kg) offered 20, 60, and 100% protection against pentylenetetrazole (100 mg/kg, i.p.)-induced convulsions. In a similar manner to diazepam (2 mg/kg), MJ (400 mg/kg) produced a marked sedative effect as shown by decreases in the number of lines crossed and the duration of ambulation in the open field test. In contrast to diazepam (2 mg/kg), MJ (5–50 mg/kg) did not show anxiolytic effects in the EPM and light/dark transition paradigms. These findings suggest that methyl jasmonate at high doses possessed anticonvulsant properties in the pentylenetetrazole animal model of epilepsy, but did not produce anxiolytic activity in mice.     

Anti-amnesic effect of Ficus religiosa in scopolamine-induced anterograde and retrograde amnesia

Context:?Ficus religiosa Linn (Moraceae) is a variety of fig tree. Its figs are known to contain a high serotonergic content, and modulation of serotonergic neurotransmission plays a crucial role in the pathogenesis of amnesia. Thus, the present study was envisaged.

Objective:?To investigate the effect of the methanol extract of figs of Ficus religiosa (FRFE) on scopolamine-induced anterograde and retrograde amnesia in mice.

Materials and methods:?Transfer latency (TL) to the preferred niche in the elevated plus-maze (EPM) and learning avoidance of passive behavior to avoid punishment in the modified passive avoidance paradigm (MPA) served as behavioral models for the assessment of memory. Scopolamine (1?mg/kg, i.p.) was administered before training for induction of anterograde amnesia and before retrieval for induction of retrograde amnesia in both models. TL in the EPM, step down latency (SDL), number of trials, and number of mistakes in the MPA were determined in vehicle control, FRFE treated (10, 50, and 100?mg/kg, i.p.), and standard groups (piracetam 200?mg/kg, i.p.). Cyproheptadine, a non-selective 5-HT_1/2 blocker (4?mg/kg, i.p.), was administered along with the FRFE to investigate the involvement of serotonergic pathways in the anti-amnesic effect of FRFE.

Results and discussion:?FRFE resulted in a significant improvement of memory, as its treatment attenuated the scopolamine-induced anterograde and retrograde amnesia dose-dependently. Further, cyproheptadine pretreatment significantly reversed the anti-amnesic effect of FRFE.

Conclusion:?FRFE has anti-amnesic activity against scopolamine-induced amnesia, in a dose-dependent manner. Inhibition of the anti-amnesic effect of FRFE by cyproheptadine substantiates the involvement of serotonergic pathways for its activity.     

Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety

Aim:

The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT₃) receptor antagonist in experimental mouse models of anxiety.

Materials and Methods:

The anxiolytic activity of “6g” (1 and 2 mg/kg, intraperitoneally [i.p.]) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus maze (EPM), light-dark (L&D) box, hole board (HB), and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. None of the tested dose of “6g” affects the base line locomotion.

Results:

The new chemical entity “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the percentage of time spent and number of entries in open arm in the EPM test. In the L&D test compound “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the total time spent in light compartment as well as number of transitions from one compartment to other. Compound “6g” (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly (P < 0.05) increased number of head dips, whereas significantly (P < 0.05) decreased the head dipping latency in HB test as compared to vehicle control group. In addition, 6g (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores (square crossed) in OFT and there was no significant effect of 6g (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) on rearing scores.

Conclusion:

In conclusion, these findings indicated that compound “6g” exhibited an anxiolytic-like effect in animal models of anxiety.KEY WORDS: Anxiety, elevated plus maze, hole-board, 5-HT₃ receptor antagonist, open field test     

Acute effect of essential oil of Eugenia caryophyllata on cognition and pain in mice

The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The study aims to evaluate the effect of clove oil on experimental models of pain and cognition in mice. To observe the acute effects of clove oil at different doses, the elevated plus maze was used for the assessment of cognition, and the tail flick and formalin tests were used for the study of pain. The formalin test showed that clove oil (0.1?ml/kg, i.p.) demonstrated significantly reduced pain response in both the phases. The lower doses (0.025 and 0.05?ml/kg, i.p.) reduced the formalin-induced pain response significantly in the second phase only. The tail-flick test showed variable response. The dose 0.1?ml/kg, clove oil, significantly decreased the tail-flick latency at 30?min and this effect was reversed by naloxone (1?mg/kg). On the contrary, the dose 0.025?ml/kg of clove oil, at 30 and 60?min increased the mean tail-flick latency compared to control group, but this effect was not statistically significant. Yet naloxone significantly (p?相似文献   

An evaluation of the anti-inflammatory,antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models

Context: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria).

Objectives: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models.

Materials and methods: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker’s yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test.

Results: AZE (30–300?mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED₅₀ values; preemptive: 232.9?±?53.33?mg/kg; curative: 539.2?±?138.28?mg/kg). Similarly, the NSAID diclofenac (10–100?mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED₅₀: 21.16?±?4.07?mg/kg) and curative (ED₅₀: 44.28?±?5.75?mg/kg) treatments. The extract (30–300?mg/kg, p.o.) as well as paracetamol (150?mg/kg, p.o.) also showed significant antipyretic activity in the baker’s yeast-induced pyrexia test (ED₅₀ of AZE: 282.5?±?96.55?mg/kg). AZE and morphine (1–10?mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine.

Conclusion: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.     

Potential cognition-enhancing properties of S 9977 in three moenls of amnesia in the mouse

The effects of S 9977 (1,3,7-trimethyl 8-[3-(4-diethylaminocarbonyl-l-piperazinyl) 1-propyl]-3,7-dihydro(1H)2,6-purinedione hydrochloride) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg i.p.) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. S 9977 was studied in a dose range of 0.0312–16 mg/kg administered p.o. 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. S 9977 was also investigated after repeated administration (twice daily for 3 days and then 60 min before acquisition on the 4th day) using the scopolamine-induced amnesia model. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine-induced hyperactivity (activity meter test), diazepam-induced release of punished behavior (four plates test), and ECS-induced convulsion. S 9977 at low doses (0.0312–0.5 mg/kg p.o.) clearly attenuated the memory deficits induced by the three amnesic treatments after acute treatment and no tolerance was observed after repeated treatment in the scopolamine model. S 9977 did not affect either scopolamine-induced hyperactivity, diazepam-induced release of punished behavior, or ECS-induced convulsions. These results point to the specificity of S 9977's antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of different origins in humans. © 1992 Wiley-Liss, Inc.     

Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus

Context: Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae), commonly called Timur, has high medicinal value and is used ethnomedicinally for the treatment of various diseases.

Objective: To evaluate the effect of hexane extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression-like behaviour in Swiss albino mice.

Materials and methods: Mice were treated with ZAHE (100 and 200?mg/kg, p.o.) and imipramine (10?mg/kg injected i.p.) for 14?days. On 14th day of the treatment, depression-like behaviour was induced by LPS (0.83?mg/kg injected i.p.) and after 24?h of LPS administration, it was assessed by measuring behavioural parameters and biochemical estimations.

Results: Behavioural tests, including the open field test, forced swimming test, tail suspension test and sucrose preference test revealed that ZAHE (100 and 200?mg/kg, p.o.) and imipramine (10?mg/kg injected i.p.) alleviated the depression symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced alterations in the concentrations of norepinephrine and serotonin (5-HT) and inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated to be LD₅₀ >?2500?mg/kg.

Discussion and conclusions: This study showed that LPS-induced depression in mice was significantly prevented by ZAHE at both the dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering monoaminergic neurotransmitters in the brain combined with its anti-inflammatory potential. Thus, it could be an effective therapeutic against inflammation-induced depression and other brain disorders.     

Assessment of luteolin isolated from Eclipta alba leaves in animal models of epilepsy

Context: Eclipta alba (Linn) Hassk. (Asteraceae) has been reported to be a nerve tonic and has been used to treat epilepsy in folk medicine.

Objective: The present study isolates and characterizes luteolin from E. alba and evaluates its antiepileptic potential in chemically induced acute and chronic models in mice.

Materials and methods: The methanol extract (16.85% w/w) of E. alba leaves was subjected to fractionation for isolation of luteolin. In acute pentylenetetrazole (PTZ) model, luteolin (5, 10, 20?mg/kg, i.p.) was administered 30?min prior to PTZ injection (100?mg/kg) in Swiss albino mice. Kindling was induced by chronic administration of PTZ (35?mg/kg) on every alternate day (48 days). Luteolin was investigated on the course of kindling development and oxidative stress markers [reduced glutathione (GSH) and malondialdehyde (MDA)] in kindled mice.

Results: Single-dose pretreatment with luteolin (10 and 20?mg/kg, i.p.) was found to be effective in an acute PTZ model (100% protection from mortality) and it did not exhibit any effect on motor coordination at the same doses. PTZ-induced kindling was significantly (p?p?p?Discussion and conclusion: The results of the present study demonstrated that luteolin had an anticonvulsant effect in an acute PTZ model. Luteolin exhibited and inhibitory effect on the course of kindling and associated oxidative stress and hence could be a potential molecule in the treatment of epilepsy.     

Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice

Learning and memory were previously evaluated by using the elevated plus-maze test in mice. We investigated whether this method could be used for the evaluation of amnesic properties of drugs, including those which alter behavior on the first (training) trial. Six drugs of different types, scopolamine, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), diazepam, butylscopolamine, methamphetamine and haloperidol were administered before training. The transfer latency of vehicle-treated mice on retention testing was significantly shorter than that on training. The transfer latencies in mice given scopolamine (1 and 3 mg/kg s.c.), butylscopolamine (6 mg/kg s.c.), methamphetamine (2 and 4 mg/kg i.p.), or haloperidol (0.4 mg/kg i.p.) were significantly prolonged on training compared with those of the corresponding vehicle groups. However, significant prolongation of the transfer latency in the retention test, compared to the vehicle groups, was observed only in mice given scopolamine (3 mg/kg s.c.), MK-801 (0.1 and 0.15 mg/kg i.v.), diazepam (4 mg/kg i.p.), or methamphetamine (4 mg/kg i.p.). These results suggested that the prolongation of the transfer latency on retention testing in the plus-maze method might be used as an indicator for impairment of learning and memory induced by the drugs which have amnesic properties, and is not related to the change in transfer latency on training.     

Antagonism of diazepam against central anticholinergic drug-induced hyperactivity in mice: Involvement of a GABA mechanism

In mice tested for 30 min in photometer activity boxes , an increased activity (hyperactivity) was observed after intraperitoneal administration of benztropine (8 mg/kg), scopolamine (2 mg/kg), atropine (24 mg/kg) and trihexyphenidyl (8 mg/kg). Such hyperactivity was reduced or suppressed by diazepam (0.5, 1 or 2 mg/kg i.p.). At these doses no reduction of spontaneous activity was found with diazepam. Picrotoxin (1 or 2 mg/kg s.c.), but neither thiosemicarbazide (4–64 mg/kg s.c.) nor strychnine (0.25 and 0.5 mg/kg s.c.) antagonized the inhibitory effects of diazepam on each anticholinergic drug-induced hyperactivity. Picrotoxin (0.5, 1 or 2 mg/kg) did not modify the decreased spontaneous activity elicited by diazepam (4 mg/kg). These results suggest that diazepam may exert its antagonistic effect on the hyperactivity induced by anticholinergic drugs through a link with the γ-aminobutryic acid (GABA) system and more precisely through direct stimulation of GABA receptors. However, since picrotoxin did not modify the reduction of the spontaneous activity induced by diazepam, one can assume that diazepam-elicited decreased activity does not involve a GABA-ergic component and furthermore does not fully determine the effects of this benzodiazepine against the hyperactivity induced by anticholinergic drugs.     

Alterations in brain amino acid metabolism and inhibitory effects on PKC are possibly correlated with anticonvulsant effects of the isomeric mixture of α- and β-amyrin from Protium heptaphyllum

Abstract

Context: α- and β-Amyrin (AMY) from Protium heptaphyllum (Aubl) March (Burseraceae) is found in Brazil and used in diverse inflammation-related diseases. This species presents a central action, as previously described.

Objective: The objectives were to evaluate the anticonvulsant effect of AMY in mice and to verify the mechanism of action.

Material and methods: Seizures were induced by pentylenetetrazole followed by acute or subchronic treatments (5–25?mg/kg, p.o. and i.p.) and determination of brain amino acids (10 and 25?mg/kg, i.p., 7?d).

Results: In the acute treatment, AMY (10, 25, and 50?mg/kg, p.o.) increased the latency to the first convulsion (FC) by 30, 44, and 40% and time to death (TD) by 36, 52, and 42%, respectively. When administered intraperitoneally, the same doses increased FC by 62, 75, and 73% and TD by 76, 82, and 119%, respectively. Combined with polymixin or staurosporine, AMY (25?mg/kg, i.p.) increased TD by 61 and 63%, respectively, as related to each drug alone. When subchronically administered (25 and 50?mg/kg, i.p.) increased FC by 75 and 101% and TD by 86 and 124%, respectively. AMY increased taurine (116 and 76%) and tyrosine concentrations (135 and 110%) in basal ganglia and hippocampus, respectively, and decreased by 68, 65, and 62% glutamate, aspartate, and GABA in basal ganglia.

Conclusion: Thus, the AMY anticonvulsant activity is related to the GABAergic system and may be linked to the inhibition of the signaling cascade of PKC as well as to alterations in amino acids metabolism.     

Improvement of cognitive functions by the acetylcholine releaser SM 21

The effect of administration of SM 21 on memory processes was evaluated in the mouse passive avoidance and in the rat social learning tests. SM 21 (10–20 mg kg⁻¹ i.p.) prevented amnesia induced by scopolamine and dicyclomine as tested by the mouse passive avoidance test and prevented memory disruption by AF‐64A and benehexol ascertained by the rat passive avoidance test. Both SM 21 enantiomers were able to abolish dicyclomine‐induced amnesia in mice. SM 21, starting from the dose of 10 mg kg⁻¹ i.p., antagonized the memory impairment produced by mecamylamine, baclofen, and diphenhydramine in mice, as well as amnesia induced by diazepam in rats. SM 21, at doses ranging between 10 and 30 mg kg⁻¹ i.p., prevented memory reduction in mice by hypoxia in the passive avoidance test. In the social learning test, SM 21 (10 mg kg⁻¹ i.p.) injected in adult rats reduced the duration of active exploration of a familiar partner in the second session of the test. SM 21 prevented amnesia in both mice and rats comparable to that of the cholinesterase inhibitor physostigmine (0.2 mg kg⁻¹ i.p.), the M1 selective agonist AF‐102B (10 mg kg⁻¹ i.p.), and the nootropic drug piracetam (30 mg kg⁻¹ i.p.). These results demonstrated the ability of SM 21 to modulate memory functions and suggests that SM 21 could be useful in the treatment of cognitive deficits. Drug Dev. Res. 47:118–126, 1999. © 1999 Wiley‐Liss, Inc.     

Huperzine A ameliorates the impaired memory of aged rat in the Morris water maze performance

AIM: To determine the memory-improving properties of huperzine A in aged rats with memory impairments naturally occurring or induced by scopolamine. METHODS: Morris water maze was used to investigate the effects of huperzine A on the acquisition and memory impairments. RESULTS: During 7-day acquisition trials, aged rats took longer latency to find the platform. Huperzine A (0.1-0.2 mg/kg, s.c.) could significantly reduce the latency. In the probe trials on the eighth day, huperzine A (0.1, 0.2 and 0.4 mg/kg, s.c.) significantly increased the time in the quadrant where plateform had disappeared in aged rats. In the acute experiment, scopolamine (0.1 mg/kg, i.p.) significantly impaired spatial memory in the trained aged rats. Huperzine A (0.4 mg/kg, s.c.) significantly reversed the memory deficits induced by scopolamine. CONCLUSION: Huperzine A ameliorates the impaired memory naturally occurring or induced by scopolamine in aged rats.