beta-Endorphin administration increases hippocampal acetylcholine levels.

The contents of acetylcholine and choline were determined in rat cortex, striatum, and hippocampus following intraventricular injection of β-endorphin or D-Ala²-enkephalinamide, a synthetic enkephalin analog, in doses known to produce analgesia in experimental animals. These opiate polypeptides produced significant increases in acetylcholine levels in the hippocampus, a subcortical structure rich in cholinergic terminals. The acetylcholine content of the hippocampus (but not the cortex or striatum) was significantly elevated 15, 30, and 60 minutes after a single intraventricular injection of β-endorphin (10 μg/brain) or D-Ala²-enkephalinamide (10 μg/brain). Peak alterations in regional acetylcholine concentrations and in analgetic effectiveness both occurred 30 minutes after peptide administration. Choline concentrations were unchanged by any of the experimental treatments. Naloxone hydrochloride (1 mg/kg, subcutaneously) affected neither brain acetylcholine concentrations, nor the response latencies of rats placed on a hot-plate; it did, however, antagonize the changes in these parameters caused by β-endorphin or D-Ala²-enkephalinamide. These data suggest that endorphins may normally regulate the physiologic activity of some cholinergic neurons.     

Chronic cannulation for intermittent intravenous fluid administration.

A system is described for rapid and effective venous cannulation for long-term administration of fluids in rabbits. This method is completely free of any harness or sling-type apparatus and in no way interferes with the normal mobility of the animal. The animals maintained in this way have participated in programs of tri-weekly administration (2-3 ml/dose) of fluid for as long as 5 mo.     

Neurophysiological effects of intracerebroventricular administration of urocortin.

The recently isolated Corticotropin Releasing Factor (CRF) related peptide, urocortin, has been reported to elicit a different behavioral profile than that of CRF. CRF is a potent anxiogenic agent and stimulant of motor activity whereas under similar conditions urocortin is a potent anorectic and mild locomotor stimulant. The neurophysiological effects of this newly synthesized peptide have not yet been examined. The present study evaluated the effects of intracerebroventricular administration of 3 doses of urocortin on the electroencephalogram (EEG) and on Event-Related Potentials (ERPs) in rats. Twenty male Wistar rats were implanted with electrodes in the amygdala and dorsal hippocampus, a cannula into the lateral ventricle, and skull surface electrodes over the frontal and parietal cortices. Following recovery from surgery, urocortin (0.01-1.0 microg) was infused into the lateral ventricle 5 min prior to the recording of EEG (10 min) and ERPs (10 min). Urocortin at any of the doses, did not produce any electrographic or behavioral signs of seizure activity. The predominant effect of urocortin infusion on EEG spectral activity was an increase in mean power in the 4-16 Hz range in the frontal cortex and a decrease in EEG stability in the frontal cortex and amygdala. Urocortin administration also decreased the latency of the P3 component of the ERP in the amygdala and hippocampus. These neurophysiological effects, that only partially overlap with those of CRF, are consistent with the behavioral profile described following urocortin administration in rats. Overall, these data further support the assertion that urocortin functions as a mild CNS stimulant enhancing arousal, as measured by EEG, and modulating the speed of stimulus evaluation as measured by ERPs.     

Systemic administration of calcitonin through ocular route.

Calcitonin has been used clinically to treat hypercalcemia, Vitamin D intoxication, osteolytic bone metastases and increased skeletal remodeling in Paget's disease. In general calcitonin is given every 6 to 12 hrs intramuscularly or subcutaneously. It has been found in this study that the same results can be achieved by giving calcitonin through eyes as ophthalmic solutions. When 25 microliters of 0.05% calcitonin was given as eyedrops to New Zealand white rabbits, it did not reach the concentration achieved by i.v. administration at the same dose level. The systemic absorption of calcitonin did not reach the level achieved by i.v. administration even though the eyedrop concentrations were increased 2-fold (0.1%) to 10-fold (0.5%). When absorption enhancers such as BL-9 and Brij-78 were added to calcitonin eyedrops, however, the systemic absorption of calcitonin was enhanced markedly. BL-9 (0.5%) increased calcitonin (0.5%) absorption 16-20 fold and raised blood concentration of calcitonin above levels achieved by i.v. injection (25 microliters, 0.05%) with 0.5% calcitonin eyedrops instillation. Effects of Brij-78 (0.5%) were even more impressive. It increases calcitonin absorption 22-24 fold and raised the blood concentration of calcitonin above the levels achieved by i.v. injection (25 microliters 0.05%) with 0.15% and 0.5% calcitonin eyedrops instillation. These results indicate that the therapeutic level of calcitonin can be reached through the ocular route.