Pentylenetetrazole-induced changes in cerebral energy metabolism in Tupaia glis.

The convulsant pentylenetetrazole was administered to the lower primate, the tree shrew. Shortly after the onset of seizures, the animals were killed using a microwave device at 25 Kw and 915 MHz. The energy metabolites glycogen, glucose, ATP, and phosphocreatine were measured in five layers of the cerebral cortex and three layers of the cerebellum. Results showed that, as compared with controls, seizing animals had decreased energy metabolites selective to certain layers. Glucose was decreased in all cortical layers, but only in the granular layer of the cerebellum. Phosphocreatine was decreased in the outer small pyramidal layer and the polymorphous layer of the cortex but was unchanged in the cerebellum. ATP was decreased only in the outer small polymorphous layer of the cortex. These changes are consistent with the concept that selective changes may occur during seizures and that these changes are localized to layers that contain pyramidal cells. Examination of whole cortex may mask more subtle regional changes.

Mecamylamine, but not atropine, antagonizes nicotine-induced hyperglycemia and potentiation of hypnosis produced by pentobarbital in mice.

An anesthetic dose of 50 mg/kg (i.p.) sodium pentobarbital caused a 61% increase in blood glucose levels in mice. Nicotine (2.5 mg/kg) given intraperitoneally 15 min prior to the sodium pentobarbital treatment further increased hyperglycemia by 29% over pentobarbital alone and 90% higher than the control. Mecamylamine (0.5 mg/kg) given intraperitoneally 15 min prior to nicotine resulted in blood glucose concentrations near the control value. Atropine (2 mg/kg) administered intraperitoneally did not prevent the hyperglycemia induced by nicotine and pentobarbital. No significant correlation was observed between the sleep time and the blood glucose of the unconscious or awake mice. However, a significant correlation was observed between the blood glucose concentration of the sleeping and awake mice. Blood glucose levels were always higher when the neuronal activity was depressed and were lower when the neuronal activity was increased.

Cerebral acetylcholine and energy metabolism changes in acute ammonia intoxication in the lower primate Tupaia glis.

Ammonia levels are elevated in many patients with hepatic encephalopathy. This observation, coupled with animal studies showing an encephalogenic role for ammonia, has led to the concept that ammonia is an important toxin in the production of neurologic symptoms. Studies in rodents have shown that ammonia alters cerebral energy metabolism in the reticular formation, an area important in the modulation of consciousness. Our study was undertaken to extend these observations to the lower primate Tupaia glis, the tree shrew. The energy metabolites glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine were measured in the reticular formation by microanalytic techniques and enzymatic cycling. Acetylcholine was measured in brain regions by gas chromatography. Acetylcholine levels were increased significantly only in the medulla-pons and diencephalon in the coma stage. The energy metabolites glucose, glycogen, and phosphocreatine were decreased in reticular formation cells during the coma, whereas lactate was increased. During the precoma, glycogen and phosphocreatine were decreased. It appears, therefore, that the tree shrew has a metabolic response to ammonia similar to that of mice. A lowering of energy metabolism in the area of brain-regulating consciousness may act to place the animal in a coma. This coma in turn acts to decrease overall metabolic demand, which allows the animal an opportunity to conserve its threatened energy reserves.

Evaluation of microwave irradiation technique to quantitate acetylcholine in the diaphragm.

This report evaluates rapid enzyme inactivation prior to acetylcholine quantitation in the diaphragm. Methods of sacrifice were decapitation and microwave irradiation. Six-hundred millisecond exposure to microwave irradiation was sufficient to raise diaphragmatic temperature to 91 degrees C and inactivated 90% of the acetylcholinesterase enzyme. The acetylcholine content of the diaphragm was found to be 3.0 nmol/g, independent of the method of sacrifice. The postmortem changes observed in brain acetylcholine content following decapitation did not occur in the diaphragm.

Nicotine potentiates sodium pentobarbital but not ethanol induced sleep.

Nicotine potentiates, in a dose dependent manner, the sleep time induced by sodium pentobarbital but not by ethanol. Mecamylamine, a nicotinic receptor antagonist, blocked the nicotine induced increase in sleep time. Atropine itself reduced sleep time but did not change the nicotine effect. It is hypothesized that the central and the peripheral nicotinic receptors play an important role in potentiating sodium pentobarbital induced sleep time.

Effect of short electromagnetic pulses on brain acetylcholine content and spontaneous motor activity of mice.

Mice were exposed to a single 15-ms or 25-ms pulse of 2,450-MHz microwaves which increased brain temperature by 2 degrees C or 4 degrees C, respectively. Immediately after exposure, the mice became hypokinetic but began recovering within 5 minutes. The 25-ms pulse (18.7 j deposited in the brain) caused a significant decrease in acetylcholine content of the whole brain, probably owing to increased permeability of the membrane.

Involvement of the cholinergic system in the precocious puberty caused by estradiol in immature female rats.

Subcutaneous administration of 0.05 mug estradiol benzoate to sexually immature female rats caused precocious ovulation and a decreased acetylcholine content in the hypothalamus and the amygdala. A higher dose of estradiol benzoate, 2 mug/rat, did not stimulate ovulation but did cause a further decrease in the acetylcholine content in the hypothalamus and the amygdala. The steady state levels of acetylcholine in the hippocampus and the striatum were unchanged with either dose of estradiol. These observations suggest a relationship between the occurrence of ovulation and the decrease in the steady state level of acetylcholine in the hypothalamus and amygdala in sexually immature rats after estradiol treatment.

Magnesium deficiency: brain acetylcholine and motor activity.

Deprivation of magnesium ion in the diet caused a significant decrease in whole brain acetylcholine content. At the reginal level, the most pronounced effect was seen in the corpus striatum, diencephalon and cerebellum. The rate of depletion and recovery varied from region to region, and what appeared to be a return to normal acetylcholine in whole brain was the total of regions either higher or lower than control. The data presented here suggest that a positive relationship exists between the lowered cholinergic activity in the corpus striatum and increased nocturnal spontaneous motor activity.

Regional acetylcholine content in mouse brain after morphine tablet implantation.

Implantation of a 75 mg morphine tablet in mice caused a significant decrease in the body weight and hypothermia. After 3 days, the concentration of acetylcholine decreased in all brain regions with the exception of the cerebellum. A significant decrease in acetylcholine content was observed in the midbrain, corpus striatum and the cerebral cortex 3 days after implantation. It is postulated that the decrease in Ach content is due to an increased release of acetylcholine as a result of development of tolerance to morphine.

Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions.

Microwave irradiation of 6 kw at 2450 MHz for 300 msec was sufficient to completely inactivate mouse brain cholinesterase and choline acetyltransferase. After this method of sacrifice, the acetylcholine contents of mouse brain regions, given in nanomoles per gram, were found to be: striatum, 81; medulla-pons, 44; diencephalon-midbrain, 34; hippocampus, 31; cerebral cortex, 26; and cerebellum, 17. Sodium pentobarbital caused a dose-dependent increase in whole brain acetylcholine. A maximal increase of 81% in whole brain was seen at 15 minutes with 80 mg/kg of sodium pentobarbital. The increase in acetylcholine after sodium pentobarbital treatment was not caused by anoxia from respiratory depression or by hypothermia. All brain regions except the cerebellum exhibited an increase in acetylcholine after pentobarbital treatment. Fifteen minutes after treatment, cerebellar acetylcholine was significantly decreased. However, at the time when half of the animals had regained the righting reflex, the unconscious mice showed an increase in cerebellar acetylcholine which was statistically significant as compared to control. The relative accumulation rate of acetylcholine calculated for cerebral cortex and hippocampus was higher than that for striatum although the absolute rate of accumulation of ACh was higher in the striatum. Thus, after sodium pentobarbital treatment, the cerebral cortex and hippocampus exhibit a greater cholinergic response than the striatum.

Dichlorvos and the cholinergic system: effects on cholinesterase and acetylcholine and choline contents of rat tissues.

The inhibition of cholinesterase by 50 mg/kg/5 ml, p.o., dichlorvos and subsequent recovery of enzyme activity was uniform in all brain regions studied. This uniformity was not observed in liver, erythrocytes and plasma. Acetylcholine levels were elevated in brain areas from 48 to 171% at 15 minutes after treatment. However, a biphasic effect was seen on choline metabolism in the brain. The cortex was found to be more cholinergic than the striatum in terms of per cent increase in acetylcholine and choline.