THE EFFECT OF OCTREOTIDE ON KAINATE-INDUCED WET DOG SHAKES AND SEIZURE ACTIVITY IN MALE AND FEMALE RATS

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity. There are sex differences in seizure susceptibility as well as in SS and NO activities in brain. The present study was undertaken to assess the effect of octreotide (OC), a stable SS analogue, on KA-induced WDS and seizures in rats, with emphasis on possible sex differences. WDS and seizures were induced by KA in male and female (proestrus) Sprague Dawley rats; OC or saline was injected 30 min before KA and the behavior was monitored for 120 min after KA. Octreotide increased the number of WDS and decreased the number of convulsions; this effect was more pronounced in males. Onset of KA-induced seizure ac tivity was earlier in females than males; however, there was no effect of OC on seizure latency. Seizure activity started after the termination of WDS. These results show OC has opposite effects on WDS and convulsions, in that it stimulates the former and inhibits the latter. These results support our previous findings that WDS and seizure activity involve separate mechanisms and suggest that WDS may have an inhibitory effect on limbic seizures.     

ACCUMULATION OF 3H-1-LYSINE BY BRAIN AND PLASMA IN MALE AND FEMALE RATS TREATED ACUTELY WITH MORPHINE SULFATE

Adult male and female Wistar rats were injected with a single dose of 40 mg/kg of morphine sulfate via indwelling intrajugular cannulas and killed two hours later. ³H-1-lysine was injected at various time intervals before the death of the animals. The distribution of the labelled amino acid was then determined in the free amino acid and lipid-nucleoprotein-extracted protein fractions of plasma and cerebral grey matter. The accumulation of ³H-activity was also determined in various areas of the brain, dorsal root ganglia, pectoral muscle and liver. Morphine-treatment produced an elevation of free ³H-lysine levels in plasma and cerebral grey matter and a decrease in incorporation into protein. A significant sex difference was noted, such that in control males the plasma free ³H-lysine and protein fractions were higher than in females. In the morphine-treated group the values obtained from males were lower than for females. In cerebral grey matter, the free ³H-lysine was significantly lower in control and morphine-treated males than in females. In the protein fraction, such sex differences varied with the time elapsed after injection of amino acid and did not clearly favor either sex. The accumulation of ³H-activity in tissue blocks taken from various regions of CNS was unaffected by morphine-treatment in subcortical components. The values were generally higher in females. ³H-accumulation was significantly altered in cortical components in the male group. In cerebral white matter, the morphine-treated males showed significant elevations of accumulation. Females showed an elevation of ³H-accumulation in the morphine-treated group only when the data was subjected to a group comparison. In the peripheral nervous system, ³H-accumulation was significantly depressed by morphine-treatment only in males. The female values were again significantly higher than those from the males. The male liver demonstrated a significant depression in accumulation of ³H-activity in the morphine-treated group. Liver tissue from females was less responsive and had higher uptakes than in males. Skeletal muscle showed no alteration in ³H-accumulation after morphine treatment in either sex.     

THE EFFECT OF NALOXONE AND MORPHINE ON 3H-1-LYSINE IN VIVO INCORPORATION INTO VARIOUS NEURONS SEPARATED FROM FIXED RAT BRAIN PREPARATIONS BY ULTRASONIFICATION: A COMPARISON OF MORPHINE EFFECTS BETWEEN WISTAR AND SPRAGUE-DAWLEY RATS

A procedure is described where by ultrasonification one can separate large neurons from their surrounding neuropil from either unfixed brain and peripheral ganglion or from similar tissue fixed in 10 per cent neutral formalin for prolonged periods. The availability of such a technique permits one to readily assess the accumulation of ³H-labeled protein precursors into a wide variety of neurons, utilizing standard liquid scintillation techniques. The separation technique has been applied in this report to determine the effects of morphine, morphine plus naloxone, naloxone given alone and saline on the accumulation of ³H-1-lysine into ventral horn, Purkinje and dorsal root ganglion neurons in Sprague-Dawley rats. The data from the control and morphine-treated animals has then been compared with similar data previously obtained from Wistar rats. In Sprague-Dawley rats, morphine had no effect on ³H-1-lysine accumulation into ventral horn neurons and stimulated accumulation into Purkinje and dorsal root ganglion neurons. Naloxone stimulated lysine accumulation into dorsal root ganglion and ventral horn neurons, but had equivocal effects on Purkinje neuron ³H-lysine accumulation. When Wistar and Sprague-Dawley rats were compared, marked differences in the effect which morphine had on lysine accumulation into neurons were noted between the two strains of rat. Ventral horn and dorsal root ganglion neurons from Wistar rats had markedly higher levels of accumulation in both control and morphine-treated rats than were observed in the Sprague-Dawley animals. With Purkinje neurons, accumulation levels between the two strains overlapped each other. Morphine inhibited lysine accumulation in Wistar Purkinje neurons but stimulated it in the Sprague-Dawley animals. The profiles of the accumulation curves from two rat strains suggest that there are not only differences in rates of uptake of ³H-lysine into protein followed by degradation between various types of neurons, but differences between the two strains as well.