Life sciences
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We administered methylnaltrexone, a peripheral opioid receptor antagonist, to guinea pigs previously injected with morphine sulfate to determine whether the compound could block opioid-induced cough suppression without blocking antinociception. The effects of methylnaltrexone (2.0, 1.6, 0.8 mg/kg) and of naltrexone (0.32, 0.16, 0.02 and 0.01 mg/kg) were compared in animals who had been injected with morphine sulfate (8.1 mg/kg). ⋯ Our results suggested that methylnaltrexone possesses opioid antagonist activity in receptors peripheral to the blood-brain barrier. Its peripheral activity makes methylnaltrexone a clinically interesting agent for maintaining the cough reflex in those who must take opioids for analgosia.
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Topiramate, a structurally novel anticonvulsant, and phenytoin were evaluated in a rat model of ischemia-induced epilepsy. In this model a transient global cerebral ischemia is induced by cardiac compression. By precisely controlling the experimental conditions the procedure causes reproducible neurological deficits that include audiogenic epileptic seizures. ⋯ Calculated ED50 values for topiramate 1 hr after oral administration were 8.2, 13.0 and 36.1 mg/kg for blockade of tonic extension seizures, clonic seizures and wild running, respectively. Corresponding ED50 values for phenytoin were 5.0, 10.8 and 20.7 mg/kg. These results support the concept that the anticonvulsant activity of these drugs is due primarily to an ability to block the spread of seizures.
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Comparative Study
Effects of tacrine (THA) on spatial reference memory and cholinergic enzymes in specific rat brain regions.
Cognitive function of rats treated with saline (control), THA (8 mg/kg, i.p.), scopolamine (5 mg/kg, i.p.), or a combination of THA (8 mg/kg) and scopolamine (5 mg/kg) was tested in the Morris water maze. The latency to find the platform in the water maze was used to evaluate performance. THA did not significantly alter the latency period as compared to control rats. ⋯ THA administration resulted in a significant decrease in AChE activity (p<0.001) in cortex (62% decrease), hippocampus (78% decrease), and hypothalamus (90% decrease). When tacrine was administered with scopolamine, a significant increase was found in the cortex (197% increase) and the hippocampus (207% increase). In conclusion, the increase in ChAT activity produced by tacrine may in part explain its ability to reverse the scopolamine induced decrease in spatial reference memory and may play a role in its beneficial effect in improving cognitive ability.
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Comparative Study
Blood glucose and prolactin in hyperprolactinemic rats exposed to restraint and surgical stress.
The effects of chronic hyperprolactinemia on plasma prolactin (PRL) and glucose were investigated in male rats submitted to two different types of stress: restraint (60 min in a plastic tube) or surgery (laparotomy under ether anesthesia). Hyperprolactinemia was induced by grafting one homologous pituitary gland under the kidney capsule. Restraint stress induced a marked increase of plasma PRL of control rats with a peak at 15 min (increase of 403%), but did not change the PRL levels of hyperprolactinemic rats. ⋯ Grafted rats presented hyperglycemia during all the experimental period, whereas control rats showed glycemia similar to basal levels by the end of the experiment. In conclusion, different responses are induced depending on the type of stress: more intense PRL secretion is induced by restraint and higher hyperglycemia by surgery. Chronic hyperprolactinemia induced a higher (restraint) or longer lasting (surgery) hyperglycemic response in the rat, adding new evidence for a diabetogenic effect of PRL.