RESUMEN
Derangements of neuroimmune, neurotrophic and neurochemical homeostasis have important implications in psychosocial stress-induced psychopathologies. Whether quercetin, a neuroactive compound, protects against psychosocial stress-induced psychiatric disturbances particularly via neurochemical mechanisms remain less well elucidated. Therefore, we further investigated the putative neurochemical as well as other cellular mechanisms of quercetin on social-defeat stress (SDS) model of psychosocial impairments. Saline (10 mL/kg,i.p.), quercetin (25, 50 and 100 mg/kg,i.p.) and ginseng (50 mg/kg,i.p.) were given to intruder mice for 14 days. From days 7-14, ten minutes of aggressive-resident-induced SDS (physical and psychological) were conducted thirty minutes after treatments. Subsequently, behavioral assessments: open-field, light/dark board, Y-maze, novel-object recognition, social-interaction and tail-suspension tests were conducted on day 14. Adrenal weight and glucose levels were measured. Monoamines, brain-derived neurotrophic factor (BDNF), corticosterone, inflammatory cytokines (TNF-α, IL-6) and executioner caspase-3 concentrations were determined in specific brain regions by ELISA. Oxidative/nitrergic stress and cholinergic markers were determined with UV-spectrophotometry. Psychosocial stress-induced anxiety, depression and cognitive defects were improved by quercetin. The decreased serotonin in the prefrontal-cortex and dopamine in the striatum, elevated levels of noradrenaline and acetylcholinesterase in the prefrontal-cortex and hippocampus with corresponding decrease in BDNF were reversed by quercetin. Quercetin reduced SDS-induced increased neuronal inflammation, caspase-3 activity, malondialdehyde, nitrite levels, but increased antioxidant activities in the three brain regions. Adrenal hypertrophy, increased serum glucose and corticosterone release were reduced by quercetin. Our findings showed that quercetin attenuates psychosocial stress-induced passive coping behavior via normalization of HPA-axis, modulation of neurochemical release, enhancement of BDNF, and inhibition of brain oxidative/nitrergic stress, neuroinflammation and apoptotic pathway.
Asunto(s)
Acetilcolinesterasa , Quercetina , Acetilcolinesterasa/metabolismo , Adaptación Psicológica , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratones , Estrés Oxidativo , Quercetina/farmacología , Estrés Psicológico/metabolismoRESUMEN
The antiretroviral is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1. This study was undertaken to investigate the effect of nevirapine (NVP) administration on gastric acid secretion, pepsin secretion, mucosal secretion, intestinal motility, and transit using apparently healthy albino Wistar rats. Eighty albino Wistar rats (50125 g body weight) from the start of the experiment were used for the study. Rats in the control group were fed normal rodent chow, while the NVP group was fed by gavage NVP (0.4 mg/kg body weight) two times daily (07:00 and 18:00 hours) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. Mean basal gastric output and peak acid output following histamine administration in the NVP-treated group were significantly higher (p < 0.001, respectively) compared to the control. Following cimetidine administration, there was significant decrease (p < 0.001) in peak acid output in the NVP-treated group compared to the control. The concentration of gastric pepsin, adherent mucus secretion, and mean value for ulcer score were significantly higher (p < 0.001) compared to their control group, respectively. There were significant increases (p < 0.05, respectively) in intestinal motility and basal contraction (p < 0.05) and increase in intestinal transit of the ileum of NVP-treated rats compared to their control, respectively. Results of the study suggest that NVP administration might provoke gastric ulceration in rats which may be caused by high pepsin, high basal acid output, and increased intestinal motility and transit (AU)
Asunto(s)
Animales , Ratas , Antirretrovirales/farmacocinética , Nevirapina/farmacocinética , Motilidad Gastrointestinal , Úlcera Gástrica/inducido químicamente , Pepsina ARESUMEN
The antiretroviral is a non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1. This study was undertaken to investigate the effect of nevirapine (NVP) administration on gastric acid secretion, pepsin secretion, mucosal secretion, intestinal motility, and transit using apparently healthy albino Wistar rats. Eighty albino Wistar rats (50-125 g body weight) from the start of the experiment were used for the study. Rats in the control group were fed normal rodent chow, while the NVP group was fed by gavage NVP (0.4 mg/kg body weight) two times daily (07:00 and 18:00 hours) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. Mean basal gastric output and peak acid output following histamine administration in the NVP-treated group were significantly higher (p < 0.001, respectively) compared to the control. Following cimetidine administration, there was significant decrease (p < 0.001) in peak acid output in the NVP-treated group compared to the control. The concentration of gastric pepsin, adherent mucus secretion, and mean value for ulcer score were significantly higher (p < 0.001) compared to their control group, respectively. There were significant increases (p < 0.05, respectively) in intestinal motility and basal contraction (p < 0.05) and increase in intestinal transit of the ileum of NVP-treated rats compared to their control, respectively. Results of the study suggest that NVP administration might provoke gastric ulceration in rats which may be caused by high pepsin, high basal acid output, and increased intestinal motility and transit.
Asunto(s)
Nevirapina/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Úlcera Gástrica/inducido químicamente , Estómago/efectos de los fármacos , Administración Oral , Animales , Cimetidina/farmacología , Ácido Gástrico/metabolismo , Determinación de la Acidez Gástrica , Mucosa Gástrica/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Histamina/farmacología , Pepsina A/metabolismo , Ratas , Ratas Wistar , Estómago/patología , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologíaRESUMEN
Most antipsychotics interfere with the dopaminergic system, resulting in extrapyramidal effects. This study compared the extrapyramidal effects of chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res), used as antipsychotics, in mice. Ninety age-matched male CD-1 strain of mice (25-33 g body weight) were divided into 3 groups, each consisting of 5 subgroups (n = 6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. Locomotor behaviour (open field test) and motor coordination (acceleratory rotarod) were assessed. Mice were also observed for 10 min for tremor and vacuous chewing movement (VCM). CPZ and Res dose-dependently decreased locomotor behaviour and impaired motor coordination (p < 0.01). RV also decreased locomotor behaviour (4.0 mg/kg; p < 0.05) but had minimal effect on motor coordination. VCM was lower in the RV group (0.17 ± 0.16/10 min) than the Res (6.8 ± 1.36/10 min) and Cpz groups (7.83 ± 1.95/10 min): F ((4,25)) = 10.703; p < 0.01. The frequency of bouts of tremor was also lower in the RV group (1.17 ± 0.72/10 min) than the Res (21.2 ± 5.63/10 min) and Cpz (7.83 ± 1.59/10 min) groups: F ((4,25)) = 11.012; p < 0.001. The root bark extract of R. vomitoria, therefore, has great potential in the management of psychotic disorders.
Asunto(s)
Antipsicóticos/química , Antipsicóticos/uso terapéutico , Clorpromazina/uso terapéutico , Extractos Vegetales/uso terapéutico , Trastornos Psicóticos/tratamiento farmacológico , Rauwolfia/química , Reserpina/uso terapéutico , Animales , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Corteza de la Planta/química , Extractos Vegetales/química , Raíces de Plantas/químicaRESUMEN
BACKGROUND: Nevirapine (NVP) is an antiretroviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in the blood. This study was undertaken to investigate the effect of chronic administration of NVP on body weight, food, and water intake using apparently healthy albino Wistar rats. METHODS: Twenty adult albino Wistar rats (50-125 g body weight) were used for the study. Rats in the control group (n=10) were fed normal rodent chow, whereas the NVP group (n=10) were fed by gavage NVP (0.4 mg/kg body weight) two times daily (07.00 h and 18.00 h) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. RESULTS: Results showed that the mean daily food and water intake in the NVP group were significantly higher (p<0.001) when compared with the control group, respectively. The mean change in body weight in the NVP group was significantly higher (p<0.001) than the control group. CONCLUSIONS: These results suggest that chronic administration of NVP may increase body weight in rats, probably due to its stimulatory effects on food and water intake.
Asunto(s)
Fármacos Anti-VIH/farmacología , Peso Corporal/efectos de los fármacos , Nevirapina/farmacología , Animales , Fármacos Anti-VIH/administración & dosificación , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Femenino , Masculino , Nevirapina/administración & dosificación , Ratas , Ratas WistarRESUMEN
AIM OF THE STUDY: Since remedies for mental disorders have been sought through both orthodox and traditional medicine this study compared the effects of the antipsychotic, chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res) in mice. MATERIALS AND METHODS: Ninety male CD-1 strain of mice (75-80 days old; 30-34 g body weight) were divided into 3 major groups and each consisting 5 subgroups (n=6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.), was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. The open field test was used to assess locomotor and exploratory behaviour, acceleratory rotarod for motor coordination, light/dark box for anxiety. RESULTS: CPZ dose-dependently decreased locomotor and exploration behaviour and impaired motor coordination (p<0.01). RV also decreased locomotor behaviour at 4.0 mg/kg (p<0.5) but did not alter exploration and motor coordination. Res however, decreased locomotion and exploration and impaired motor coordination 0.8 and 1.6 mg/kg (p<0.05). In the light/dark box, CPZ increased anxiety related behaviour at 1.0, 2.0 mg/kg (p<0.05) whereas RV dose-dependently decreased anxiety from 1.0 to 4.0 mg/kg (p<0.01). Res, unlike RV, dose-dependently increased anxiety related behaviour from 0.4 to 1.6 mg/kg. CONCLUSION: Root bark extract from Rauwolfia vomitoria produced better behavioural effects with less distortion in motor coordination when compared to chlorpromazine and so has a great potential as an alternative antipsychotic agent compared to chlorpromazine. Since Res did not produce same effects as RV, the effect of RV may not be due solely to Res as claimed.