Contrasting effects of acute and chronic treatments with ketamine on inhibitory avoidance and escape latency in the elevated-t-maze

Previous studies have suggested the involvement of N-Methyl,D-Aspartate (NMDA) pathway in the Pathophysiology of anxiety disorder. However the role of NMDA neurotransmission in the neurobiology of different classes of anxiety disorder remains unexplored. This study examined the effects of intraperitoneal administration of acute (3 mg/kg) and withdrawal from chronic administration of non-competitive NMDA receptor antagonist - ketamine (15 mg/kg daily for 21 days and withdrawn for 24 hours) on inhibitory avoidance duration (conditioned fear related behaviour) and escape latency (unconditioned fear related behaviour) using the elevated-T-maze (ETM) in mice (n = 10). The results showed that acute ketamine reduced while withdrawal from chronic ketamine administration increased inhibitory avoidance duration significantly (p < 0.05). Acute ketamine also increased escape latency, but withdrawal from chronic ketamine reduced escape latency significantly (p < 0.05). It was inferred that acute ketamine decreased conditioned and unconditioned fear related behaviours as a result of NMDA transmission downregulation, while withdrawal from chronic ketamine induced increase in conditioned and unconditioned related behaviours via NMDA transmission upregulation. Changes in NMDA transmission appear to be relevant in the neurobiology of generalized anxiety disorder and panic disorder related behaviours in the ETM, hence pharmacological modulation of NMDA transmission may contribute to improved treatment of generalised anxiety and panic disorders.Keywords : N-Methyl,D-Aspartate, upregulation, downregulation, neurotransmission

The pruritogenic effect of Anaphe venata extracts in rats: the role of cholinergic, GABAergic and opioid systems

This study sought to investigate the effect of the crude aqueous and phosphate buffer saline (PBS) extracts of Anaphe venata on body scratching behaviour in rat in a novel environment and also to determine the neural mechanism(s) involved. Aqueous and PBS extracts of Anaphe venata were prepared and their effects on body scratching behaviour were evaluated in rats. Animals were divided into four groups (n = 6-12 per group) and graded doses of extracts (100-400 mg/kg) were administered (dissolved in normal saline) intraperitoneally (i.p.) to each animal in the experimental groups. The control group received an equivalent volume of normal saline. Behavioural scores were recorded for a period of 30 minutes after the administration of normal saline or extract. The role of various receptors in the extract induced pruritus was evaluated using known receptor agonist/antagonists. Results showed that aqueous Anaphe extract induced dose-dependent increase in body scratching behaviour (

Toxicity potentials and novelty-induced behavior effects of JEDDY decoction

JEDDY decoction, a plant medicine, is prepared by the “Village Chemist” of Obafemi Awolowo University in Nigeria for the treatment of hemorrhoids, pile, flatulence, abdominal distention, indigestion and colic. It is a popular OTC herbal medicine, available in Nigeria especially in the South-west. Hence, the main objective of the research was to carry out scientific studies on its toxicity potentials as well as possible central effects. Twenty four albino rats of both sexes were obtained and divided into four groups (n=6 per group) for the administration of three dose levels of JEDDY decoction and the vehicle. In sub-chronic toxicity test, JEDDY decoction was  administered orally to rats at daily doses of 334, 667 and 1334  ìl/kg/day/30 days. Generally, their behavioral, mortality, biochemical and histopathological outcomes were evaluated. Noveltyinduced behavior (NIB) was observed on both day 1 and day 30 of administration of JEDDY  decoction and the vehicle. The animals were sacrificed on day 30 after the NIB scoring and blood sample was obtained for biochemical assays for triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate  aminotransferase (AST) and alkaline phosphatase (ALP) using the serum. These biochemical assays were also carried out on the liver obtained from rats treated with both JEDDY decoction and the vehicle, respectively. ANOVA, followed by Post hoc analysis using student Newman Keuls test was used in establishing significant levels for all the data obtained statistically. The sub-chronic administration of JEDDY decoction revealed a  dose-dependent decrease in the body weight of the treated groups but the percentage change was statistically not significant when compared with the control. The sub-chronic administration at all the three dose levels revealed no significant effect on locomotion and rearing activities when compared with the control. Acute administration of JEDDY decoction at the three dose levels (344, 667 and 1334 ìl/kg/30 days, p.o.) also revealed no significant effects on locomotion activities when compared with the control but the ANOVA revealed that there was a significant decrease in grooming activities at the dose of 667 ìl/kg only when compared with the control. Biochemical analysis showed that there was a significant decrease on triglyceride and cholesterol level due to JEDDY decoction administration when compared with the control. Furthermore, biochemical analysis showed that sub-chronic administration of JEDDY decoction caused no significant effect on ALT, AST and ALP in rats when compared with the control. Thus, oral acute and sub-chronic administration of JEDDY decoction had no significant potential toxicity effect in rats.Keywords: JEDDY decoction, herbal, toxicity, grooming, behavior

Neuropharmacological effects of Alchornea cordifolia (Schumach. & Thonn.) Mull. Arg. (Euphorbiaceae) in mice

Alchornea cordifolia (Euphorbiaceae) is a common plant, which has featured prominently in traditional medicinal practice. It has been reported that the decoction of the leaves is taken as central nervous system stimulant. This work was therefore undertaken to examine the central nervous system effects. The neuropharmacological profile of the plant was determined in mice to which the plant extract had been orally administered at respective doses of 250, 500 and 1,000 mg/kg. The behavioral models used included noveltyinduced behaviors (locomotion, rearing and grooming), holeboard and elevated plus maze (anxiolytic) and forced swimming (antidepressant). The Y-maze was used for the investigation of the plant extract on locomotion, learning and memory. The results obtained showed that both locomotor and rearing activities were significantly decreased at the highest dose of 1000 mg/kg orally, while grooming behavior was significantly decreased at all the doses administered. In the hole board experiment, the frequency of head-dips was decreased significantly at 1000 mg/kg, while there was no significant effect observed in the elevated plus maze. Y-maze model results showed that it had no significant effect on spatial memory. There was no significant difference in the immobility duration due to administration of the extract in the forced swimming test. In conclusion, the present study showed that although the ethanolic leaf extract of A. cordifolia exhibited some central inhibitory effect, it is devoid of anxiolytic, antidepressant activities and has no significant effect on learning and memory in mice.Keyword: A. cordifolia, locomotion, grooming, mice, anxiolytic, antidepressant, mic

Dual Hypocretin Receptor Antagonism Is More Effective for Sleep Promotion than Antagonism of Either Receptor Alone

The hypocretin (orexin) system is involved in sleep/wake regulation, and antagonists of both hypocretin receptor type 1 (HCRTR1) and/or HCRTR2 are considered to be potential hypnotic medications. It is currently unclear whether blockade of either or both receptors is more effective for promoting sleep with minimal side effects. Accordingly, we compared the properties of selective HCRTR1 (SB-408124 and SB-334867) and HCRTR2 (EMPA) antagonists with that of the dual HCRTR1/R2 antagonist almorexant in the rat. All 4 antagonists bound to their respective receptors with high affinity and selectivity in vitro. Since in vivo pharmacokinetic experiments revealed poor brain penetration for SB-408124, SB-334867 was selected for subsequent in vivo studies. When injected in the mid-active phase, SB-334867 produced small increases in rapid-eye-movement (REM) and non-REM (NR) sleep. EMPA produced a significant increase in NR only at the highest dose studied. In contrast, almorexant decreased NR latency and increased both NR and REM proportionally throughout the subsequent 6 h without rebound wakefulness. The increased NR was due to a greater number of NR bouts; NR bout duration was unchanged. At the highest dose tested (100 mg/kg), almorexant fragmented sleep architecture by increasing the number of waking and REM bouts. No evidence of cataplexy was observed. HCRTR1 occupancy by almorexant declined 4–6 h post-administration while HCRTR2 occupancy was still elevated after 12 h, revealing a complex relationship between occupancy of HCRT receptors and sleep promotion. We conclude that dual HCRTR1/R2 blockade is more effective in promoting sleep than blockade of either HCRTR alone. In contrast to GABA receptor agonists which induce sleep by generalized inhibition, HCRTR antagonists seem to facilitate sleep by reducing waking “drive”

Identification and Characterization of Microsporidia from Fecal Samples of HIV-Positive Patients from Lagos, Nigeria

BACKGROUND: Microsporidia are obligate intracellular parasites that infect a broad range of vertebrates and invertebrates. They have been increasingly recognized as human pathogens in AIDS patients, mainly associated with a life-threatening chronic diarrhea and systemic disease. However, to date the global epidemiology of human microsporidiosis is poorly understood, and recent data suggest that the incidence of these pathogens is much higher than previously reported and may represent a neglected etiological agent of more common diseases indeed in immunocompetent individuals. To contribute to the knowledge of microsporidia molecular epidemiology in HIV-positive patients in Nigeria, the authors tested stool samples proceeding from patients with and without diarrhea. METHODOLOGY/PRINCIPAL FINDINGS: Stool samples from 193 HIV-positive patients with and without diarrhea (67 and 126 respectively) from Lagos (Nigeria) were investigated for the presence of microsporidia and Cryptosporidium using Weber's Chromotrope-based stain, Kinyoun stain, IFAT and PCR. The Weber stain showed 45 fecal samples (23.3%) with characteristic microsporidia spores, and a significant association of microsporidia with diarrhea was observed (O.R. = 18.2; CI: 95%). A similar result was obtained using Kinyoun stain, showing 44 (31,8%) positive samples with structures morphologically compatible with Cryptosporidium sp, 14 (31.8%) of them with infection mixed with microsporidia. The characterization of microsporidia species by IFAT and PCR allowed identification of Enterocytozoon bieneusi, Encephalitozoon intestinalis and E. cuniculi in 5, 2 and 1 samples respectively. The partial sequencing of the ITS region of the rRNA genes showed that the three isolates of E.bieneusi studied are included in Group I, one of which bears the genotype B. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is the first report of microsporidia characterization in fecal samples from HIV-positive patients from Lagos, Nigeria. These results focus attention on the need to include microsporidial diagnosis in the management of HIV/AIDS infection in Nigeria, at the very least when other more common pathogens have not been detected

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Toxicity potentials of Senna podocarpa (Guill.et Perr.) Lock pods in rodents

The effects of acute (LD50) and sub-chronic doses of the aqueous infusion of Senna podocarpa (Guill. et Perr.) Lock pod on the liver, kidney, brain and testis of mice and rats were studied, respectively. The acute toxicity studies did not produce any observable lethal effects and the calculated LD50 was 6.6 g/kg. The histopathological analysis of the liver, kidney, brain and testis showed no adverse effect. Behavioral observations and the histopathological findings did not show significant differences between the control and the treated groups. There were no marked adverse alterations or degeneration of tissues since these vital organs showed normal architectures suggesting no morphological disturbances as compared with the control group. The findings indicated that the aqueous infusion of S. podocarpa pod was devoid of overt acute and sub-chronic toxic effects in mice and rats. Key words: Senna podocarpa pods, acute toxicity, sub-chronic toxicity Afr. J. Trad. Comp. Alt. Med. Vol.2(3) 2005: 274 - 28

Acute toxicity and sleep-wake EEG analysis of Stachtarpheta cayennensis (Verbenaceae) in rodents

This study was carried out in order to establish the scientific basis of the reported ethno-medicinal use of Stachytarpheta cayennensis (Verbanaceae) as sedative drug. The acute toxicity and barbituric-hypnotic test of the total aqueous (TASC), 50% ethanol (SCCR) and butanol (SCBT), ethylacetate (SCEA) fractions of dried leaves of S. cayennensis were studied in male rats and mice. The effect of systemic administration of TASC on sleep architecture in rats was also evaluated in Sprague-Dawley rats that were chronically implanted with electrodes for electroencephalogram (EEG) and electromyogram (EMG) recording. The acute toxicity test revealed no lethal effect with doses of SCCR (up to 2000 mg/kg) per oral in rats and doses of TASC (up to 1000 mg/kg and 95 mg/kg) systemically in rats and mice respectively. The extracts significantly (p < 0.01) potentiated phenobarbital-induced hypnosis by reducing sleep latency and increasing sleeping time in a dose-dependent manner. Systemic nocturnal administration of single doses (250 and 500 mg/kg) 30 minutes before the onset of dark period of TASC significantly (p < 0.05) increased total sleep time, time spent in non-rapid eye movement (NREM) sleep during the 6-h recording period while its effect on REM sleep was biphasic with the higher dose administered. The aqueous extract of Stachytarpheta cayennensis showed profound effects on sleep-wake stages suggesting the potential sedative effects. Key words: Stachytarpheta cayennensis, acute toxicity, barbituric-hypnotic test, Wake, NREM sleep, REM sleep Afr. J. Trad. Comp. Alt. Med. Vol.2(3) 2005: 222 - 23

The abusive potential of habitual consumption of the fruits of dennettia tripetala G.Baker (Annonaceae) among the people in Ondo township (Nigeria)

No Abstract.Nigerian Journal of Natural Products and Medicine Vol. 10 () 2006: pp.55-6