Corrent information from studies in animal models indicates that perinatal exposure to atcohol produces a variety of damaging consequences in the central nervous system. These mayresult from direct neurotoxic effects of ethanol on the CNS, a system known to be particularlysusceptible to environmental influences during development.

The present study was undertaken to investigate the effects of ethanol on the neuronal viability and neurite outgrowth, one of the critical steps in neuronal differentiation, in primarycultured neuronal and glial cells of rat hippocampus.

Cell cultures were prepared on embryonic day 17 (E17) for treatment with a series ofethanol concentrations (10, 100, 500, and 1000mM). Effect of ethanol was investigated at 0, 18, and 24 hour fo11owing ethanol treatment. To study the changes in proliferation of glialcells, protein content was measured at 7 day in vitro.

The results are as fo11ows :

1) Ethanol did not altered neuronal survival or attachment to the substrate at any of the concentrations that were used.

2) 10 or 100mM ethanol was associated with significant increase in the total neurite length per cell.

3) 10 or 100mM ethanol markedly increased and 1000mM ethanol decreased protein contents on 7 day in vitro.

These findings suggested that ethanol mar have distinct effects on neurite outgrowth andalso indicated that high concentration of ethanol (500~1000mM) and long period of exposure(3~7days) were required to produce toxic effects on neurons and glial cells in this system.

Insulin controls the levels of blood sugar by inhibiting glucose release from liver and by stimulating glucose utilization in muscle and adipose tissues. In addition to its peripheral effects, insulin influences circulating glucose levels by modulating glucose production and its metabolism through central nervous system. But it is presently not well known whether the central effect of insulin on plasma glucose is mediated by directly or indirectly through CNS actions. The autonomic nervous system exerts a dual control over insulin secretion. The parasympathetic nervous system can augment insulin secretion and the sympathetic nervous system can produce a net impairment of insulin release.

In the present study, we measured the changes of blood glucose and pyruvic acid level to examine the effetcs of intracisternally injected insulin. Carbachol and scopolamine in streptozotocin(STZ)-induced diabetic rats.

results are as follows:

1) streptozotocin produced significant increase in blood glucose and pyruvic acid concentrations.

2) Intracisternally injected insulin markedly reduced blood glucose and pyruvic acid concentrations in STZ-induced diabetic rats.

3) Intracisternally injected cholinominetics, carbachol, reduced blood glucose and pyruvic acid concentrations in STZ-induced diabetic rats.

4) Intracisternally injected anticholinergics, scopolamine, increased the concentration of the blood glucose and inhibited the concentration of the blood pyruvic acid in STZ-induced diabetic rats.

Therefore, it is suggested that central parasympathetic nervous system plays an partial role in modulating peripheral blood glucose metabolism and insulin produse hypoglycemic action via central parasympathetic nervous system.

PCPA is a drug which depletes serotonin by inhibiting tryptophan hydroxylase activity.

Recent evidence indicates that the ascending cholinergic projection from the basal forebrain and ascending serotonergic projections from the brain stem exert a powerful control over the generalized electrical activity of the hippocampus formation and neocortex. Cross & Dentin(1985) reported that destruction of ascending cholinergic neurons by injection of ibotenic acid into the basal forebrain results in a significant reduction in 5-HT₁ receptor in the denervated cortex.

Maura & Raiteri(1986) observed that the release of (³H) Ach was concentration depenendently inhibited by exogenous 5-HT in rat hippocampus.

So, we were interested in investigating whether PCPA which depletes the serotonin also affects the cholinergic system. The brain(cortex area 3, 4, 17 and hippocampus) were exised on the 3day and the 7day after single injection of PCPA 3mg/10µl into the cerebroventricle(Lateral ventricle AP+8.2mm ; L, 1.5mm ; DV+1.2mm).

5-HT and 5-HIAA contents were measured by HPLC-ECD and acetylcholine was measured by GC.

The results are

1) 5-HT & 5-HIAA contents in the cortex & hippocampus were decreased gradually after PCPA injection but not significant.

2) Ach contents in the cortex & hippocampus were decreased significantly on the 3rd day & 7th day after PCPA injection.

3) We observed that the cerebral cortex has small amount of vesicles or no vesicles and coated vesicles in the axon terminals by electron microscope.

So, these results suggest that PCPA treatment results in significant changes of cholinergic system in the brain.

Simonic(1988) have investigated that hypothermic effect of oholinornimetics is mediated through an activation of muscarine cholinergic receptors. And also, Yamada(1987) injected trytamine into the lateral cerebroventricle in mice and observed hypothermic through 5-HT₁ receptor.

We have previously reported that PCPA(a serotonin depletor), has reduced 5-HT contents gradually, but had a marked reduction in Ach contents in the cortex and hippocampus.

After injection of PCPA and 5,7-DHT, a serotonergic toxin into the cerebroventricle in rats, we observed the colonic body temperature and Ach contents of cerebral cortex.

The results of our study are as follows :

1) Ach contents in the cortex were decreased significantly on the 3rd day & 7th day after PCPA i.c.v. injection.

2) Ach contents in the cortex were not changed on the 3rd day & 7th day after 5,7-DHT i.c.v. injection.

3) Increase in colonic body temperature was markedly observed in rats on 3rd day & 7th day after received intracerebral PCPA injection. During handling with rectal probe insertion there is a small changes of colonic body temperature with time.

4) Increase in colonic body temperature was observed in rats on 3rd day after received intracerebral 5,7-DHT injection. During handling with rectal probe insertion there is a small changes of colonic body temperature with time.

So, we concluded that serotonin depletion could cause a decrease in Ach contents of the cortex and also increase in colonic body temperature via cholinergic system in the brain.

Brain ischemia due to a critical reduction in cerebral blood flow is a common cause of irreversible brain damage. Ischemia is invariably accompanied by an increase in tissue lactate concentration due to anaerobic metabolism of glucose and energy failure.

Despite new insights into the pathophysiologic mechanism of cerebral ischemia, the clinical therapeutics of cerebral ischemia is usually limited to agressive anticoagulation and supportive measures.

But. recently, new pharmacological agents including calcium channel blocking agent, perfluorocarbon, free radical scavenger and opiate antagonist are considered as possible therapeutic application for restoration of blood flow to areas of focal ischemia in both laboratory and clinical trials.

Naloxone, an opiate antagonist, has been reported to improve neurological function, spinal blood flow and somatosensory evoked potentials after spinal injury. Thus, Endogenous opioids might play a role in pathophysiology of central nervous system ischemia and that opiate antagonist might be of benefit in the treatment of experimental stroke.

But, on the other hand. there are many evidences that naloxone is not benefical. So use of naloxone for the treatnebt of ischemia insult is controverial.

Therefore, The present investigation was undertaken to elucidate the effects naloxone on cerebral ischemia by measurement of the cerebral energy metabolites concentration.

Cerebral ischemia was produced in spontaneously hypertensive rat(SHR) by bilateral common carotid artery ligation. Naloxone(1mg/kg) was administered intraperitoneally 30 min after the carotid artery ligation.

The results obtained were as follows :

1) There were no differences in the concentration of APT and lactete between normotensive Sprague-Dawley rats and SHR.

2) In bilateral common carotid artery ligated SHR, the concentration of APT was considerable decreased and that lactate was slightly increased.

3) Naloxon didn'y change the cerebral energy metabolism in ischemic model. These data indicated that naloxone had no benefical effect on cerebral ischemia but for definite conclusion, more controlled experiments must be performed.

After unilateral lesion of the rat neostriatum, we have been studied the relation between the behavioral chages of the rat and structural chages of the substantia nigra. We could find that a great number of axon terminals with pleomorphic vesicles in the ipsilateral substantia nigra were degenerated after one site lesion of neostriatum. while the structure of contralateral site was entirely intact. Also, we have been investigated that the contralateral asymmetry of posture and turning bebavior of the rat with lesion in the neostriatum. By the above results, it can be concluded that the axon terminal with pleomorphic vesicles in the substantia nigra ending of strio-nigral fibers and the degeneration of these ending is a cause to bring the contralateral postural asymmetry and/or circle behavior.

The effect of intraperitonelly administered higenamine on the cytochrome P -450, b₅, P-nitroanisole-O-demethylase and lipid peroxidation in the rat hepatic microsomes were determined. The following results were obtained ; 1) The intraperitonelly administered higenamine increased contents of rat hepatic microsomal cytochrome P-450 and b₅. 2) The principal role of cytochrome P-450 in mixed function oxidase reactions includes hydroxylation of various drugs, fatty acids, steroids, pesticides and carcinogens. The increased cytochrome P-450 induced by higenamine decreased on the both AAF of N-hydorxylation and Ring-hydroxylation. 3) Activity of P-nitroanisole-O-demethylase in hepatic microsomes with higenamine was decreased accorting to incresed dosage of higenamine. 4) The formation of lipid peroxides was increased according to increased dosage of higenamine.

Thyrotropin releasing hormore(TRH) administered intracerebroventricularly (i.c.v) in microgram quantities to anesthetized rabbits, produces marked stimulation of colonic motility, transit and fluid accumulation. These effects depend on an intact vagal system. Atropine blocks hypermotility but not the increased intestinal transit and fluid accumulation. The latter effects are antagonized by antiserotonin compounds. In this study, we found that pretreatment of rabbits with naloxone(2.5 mg/kg) or naltrexone(1.0 mg/kg) attenuated or blocked the TRH-induced colonic transit and increase in luminal fluid, but not the hypermotility. In this respect the narcotic antagonist effects resemble those produce by the antiserotonine compounds or opiate agonists.

Experimental handling and colonic temperature measurement have been shown to cause stress and induce a long lasting rise in colonic temperature in the rat. Injection is also a type of stress to induce hyperthermia in the rats. In the present study, no difference was found between injection group and simple handling group.

After rats were treated with CC1₄, phenobarbital and artemisia messes-schmiaiana var viridis(artemisia), hepatic microsomal cytochrome P-450, cytochrome b₅ and lipid peroxidation were investigated. When vitamin A, C and E were added incubation medium in each group respectively, lipid peroxidation was observed. The results were as follows. 1) When administrated with CC1₄ in rats, the contents of total microsomal cytochrome P-450 and cytochrome b₅ were decreased by 58% and 36%, respectively. And lipid peroxidation was decreased to by 6%. 2) When administrated with phenobarbital and artemisia. in rats respectively, the contents of total microsomal cytochrome P-450 and cytochrome b₅ were increased by 25 to 135%. And lipid peroxidation was increased by 30 to 57%. 3) When administrated with CC1₄ and phenobarbital or artemisia. in rats, the contents of total microsomal cytochrome P-450 and cytochrome b₅ were increased by 8 to 35%. And lipid peroxidation was increased by 4 to 14%. 4) When vitamin A, C and E incubated in each group in each group in vitro, lipid peroxidation were decreased by 3 to 87%. And th higher concentrations of vitamin A, C and E were, the more lipid peroxidation was decreased. These results indicate that vitamin antioxidants can prevent lipid peroxidation in CC1₄, phenobarbital, CC1₄ with phenobarital. artemisia. and CC1₄ with artemisia.-pretreated rat liver microsomes.

After animals were treatd with CCl₄, histological changes were shown in the endoplasmic reticulum, and also microsomal activity was decreased and hepatic necrosis, lipid peroxidation in the liver were repoted. Repeated administration of phenobarbital results in the induction of enzyme that metabolize a number of drugs and, Roberts and Plaa reported that bilirubin output was increased significantly after administration of phenobarbital in rats. Artemisia. was used as folk medicine for the treatment of hyperbilirubinemia. Kiku Tanni(1968) claimed that administration of Artemisia. in patient with acute hepatitis, significantly lowered the bilirubin index, S.G.O.T. and S.G.P.T. The purpose of the this report was to study the effect of CCl₄, phenobarbital. Artemisia on biliary excretion. The results obtained are summarized as follows. 1) Volume of the bile juice was decreased in CCl₄ group but increased in phenobarbital and Artemisia. group. 2) Biliary output was slightly decreased in CCl₄ group but increased in phenobarbital group. 3) Cholate output was decreased in CCl₄ group, but phenobarbital and Artemisia group was shown sighificant increase. 4) Cholesterol output was decreased in CCL₄ group, but increased in phenobarbital group. By the above results, it is felt that after treated with phenobarbital and artemisis following liver damage with CCl₄, detoxication process was shown and the liver damage were protected.