Effect of Insulin on Visuo-Spatial Memory and Histology of Cerebral Cortex in the Presence or Absence of Nitric Oxide Inhibition.

Insulin has emerged from its traditional 'peripheral' glucose-lowering function to become increasingly regarded as a brain hormone that controls a wide range of functions including learning and memory. Insulin action on learning and memory is linked to nitric oxide (NO) signalling, but its effects on memory and histology of cerebral cortex in conditions of varied NO availability is unclear. This research sought to determine the effect of insulin on visuo-spatial learning, memory and histology of cerebral cortex during NO deficiency. Twenty-four mice weighing 21-23 g, were divided into four groups (n = 6) and treated daily for seven days with 0.2 ml distilled water subcutaneously (s.c.) (control), 10 I.U/kg insulin s.c., 10 I.U/kg insulin + 50 mg/kg L-NAME intraperitoneally (i.p.), and 50 mg/kg i.p. L-NAME s.c., respectively. The 3-day MWM paradigm was used to assess memory. Brain tissue was examined for histological changes. There was no significant difference between day 1 and day 2 latencies for all the groups. The mice in all (but L-NAME) groups spent more time in the target quadrant, and the difference was significant within but not between groups. There was significant reduction in number of platform site crossings (4.83 ± 0.5, 0.67 ± 0.3, 0.50 ± 0.3 and 0.50 ± 0.3 for control, insulin, insulin+L-NAME and L-NAME groups, respectively) in all the groups compared to control. Normal histology of the cortex and absence of histological lesions were observed in brain slides of control and treatment groups. It was concluded that insulin administration impairs visuo-spatial memory to a greater extent in the presence of NO block, and to a lesser extent in the absence of NO block. Nitric oxide has a role in insulin-induced memory impairment. Insulin administration in the presence or absence of NO block had no effect on histology of cortex.

Acute Administration of Methionine Affects Performance of Swiss Mice in Learning and Memory Paradigms.

Methionine, an essential amino acid, plays an essential role in the central nervous system CNS development. It serves as a crucial intermediate in the methylation, trans-sulfuration and amino- phosphorylationpathways,necessary for the synthesis of nucleic acids, phospholipids, hormones, neurotransmitters, antioxidants, polyamines, catecholamines and other biogenic amines. The effect of methionine on learning and memory in mice was investigated using Morris water maze (MWM), Elevated plus maze(EPM) and Y maze (YM). Animals were administered with distilled water (control), methionine (1,700mg/kg); folate (3mg/kg) or methionine (1700mg/kg) plus folate (3mg/kg) for 14 days. Escape latency and time spent in target quadrants; transfer latency and percentage spontaneous alternations were measured in the MWM, EPM and YM respectively. The animals were anaesthetized with inhalational chloroform and their brains subsequently harvested, homogenized and assayed for acetylcholinesterase24 hours after the experiment.Folate significantly(p<0.05) increased transfer latency (53.33 ± 12.62) as compared to control (20.1 ± 5.01) and reduced spontaneous alternations significantly (25.0 ± 8.9) when compared to control (44.33 ± 3.07). When folate was combined with methionine there was also a significant increase in transfer latency (43.0 ± 14.39) when compared with control (20.1 ± 5.01). Folate-methionine combination also significantly reduced spontaneous alternations (20.4 ± 8.4) as compared to the control (44.33 ± 3.07) much more than folate alone. Acetylcholinesterase activities in all groups were not statistically significant. It can be concluded that acute methionine administration has some benefits in memory enhancement. However, a short course folate supplementation impairslearning and working memory especially when combined with methioninewhich may be as a result of sudden overwhelming of the methylation cycle, leading to homocysteinemia which is pro-dementia.

Evaluation of the antipsychotic potential of aqueous fraction of Securinega virosa root bark extract in mice.

Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in African traditional medicine in management of mental illness. Previous study showed that the crude methanolic root bark extract of the plant possesses antipsychotic activity. In this study, the antipsychotic potential of the residual aqueous fraction of the plant was evaluated using two experimental models, apomorphine induced stereotypic climbing behaviour and swim induced grooming, all in mice. The effect of the fraction on haloperidol-induced catalepsy was also evaluated. The fraction significantly reduced the mean climbing score at the highest dose tested (500 mg/kg). In the swim-induced grooming test, the fraction significantly and dose-dependently (125-500 mg/kg) decreased the mean number and mean duration of swim-induced grooming activity in mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p < 0.001) decreased the mean grooming episodes and duration. However, the fraction did not significantly potentiate haloperidol-induced catalepsy. These results suggest that the residual aqueous fraction of methanol root bark extract of Securinega virosa contains biological active principle with antipsychotic potential.

Psychopharmacological potentials of methanol leaf extract of Securinega virosa Roxb (Ex Willd) Baill. in mice.

Schizophrenia is a highly disabling chronic psychiatric illness. The existing antipsychotic agents are associated with untoward effects and drug interactions leading to the intensification of search for newer agents with better efficacy and safety profile. Securinega virosa is a commonly used medicinal plant in African traditional medicine. The decoction of the leaves of the plant in combination with other plants is used in the management of mental illness. In this study, we evaluate the antipsychotic potential of the methanol leaf extract (25, 50 and 100 mg kg(-1)) of the plant using apomorphine-induced stereotypic climbing behavior and swim-induced grooming tests, all in mice. The CNS depressant effect was also evaluated using ketamine-induced sleep test mice. The extract at the highest dose tested (100 mg kg(-1)) significantly reduced the apomorphine (1 mg kg(-1))-induced stereotypic climbing behavior after 30 min. Similarly, haloperidol (2 mg kg(-1)), the standard agent significantly (p<0.001) decreased the mean climbing behavior. In the swim-induced grooming test, the extract significantly (p<0.01) and dose-dependently decreased the total grooming time. Similarly, haloperidol (2 mg kg(-1)) significantly (p<0.001) decreased the mean grooming activity. The extract significantly increased the total ketamine-induced sleep duration at doses of 50 and 100 mg kg(-1). These findings suggest that the extract possesses antipsychotic and sedative potentials and lend credence to the ethnomedical use of the leaves of the plant in the management of mental illness.

Anti-nociceptive and anti-inflammatory activities of aqueous leaves extract of Ocimum gratissimum (Labiate) in rodents.

The aqueous leaves extract of Ocimum gratissimum was investigated for anti-nociceptive and anti-inflammatory effects in mice and rats. The models used to study the effect on nociception are the acetic acid-induced abdominal constriction test, hot-plate method in mice. The anti-inflammatory effect was investigated employing the formalin-induced hind-paw oedema in rats. The extract caused a significant (p<0.05), dose-dependent inhibition of acetic acid-induced writhing and hot-plate method. The extract also exhibited anti-inflammatory effect which was significant (P<0.001) at all the three doses. The intraperitoneal LD(50) value of the extract was 1264.9 mg/kg body weight in mice. Preliminary phytochemical screening revealed the presence of alkaloids, saponins, tannins and flavonoids. The results suggest the extract contained pharmacologically active principles, and supports the local application of the plant in painful and inflammatory conditions.

Anti-nociceptive and anti-inflammatory activities of ethanol extract of syzygium aromaticum flower bud in Wistar rats and mice.

The ethanol extracts of Syzygium aromaticum flower bud were tested for anti-nociceptive and anti-inflammatory effects in mice and Wistar rats which were carried out using acetic acid-induced abdominal contractions in mice and formalin-induced hind paw edema in Wistar rats. Three doses of the ethanol extract (50, 100, and 200 mg/kg body weight i.p.) were used for both studies. The extract had an LD(50) of 565.7 mg/kg body weight intraperitoneally in mice. The extracts produced significant effect (P<0.05) at all the three doses. Similarly, the anti-nociceptive activity produced significant effects (P<0.05) at all the three doses of the extract. The result supports the local use of the plant in painful and inflammatory conditions.