Age-related changes of hippocampal alpha 1- and alpha 2-adrenoceptors were investigated using intraocular hippocampal transplants combined with 3H-prazocin and 3H-para-aminoclonidine (3H-PAC) autoradiography. Young hippocampal grafts in young hosts and old grafts in old hosts innervated by noradrenergic sympathetic fibers were studied. In addition, young and old hippocampal grafts were examined following noradrenergic denervation by superior cervical ganglion removal. The 3H-PAC binding was significantly reduced in aged grafts as compared to young grafts whereas the 3H-prazocin binding did not change with age. After sympathetic denervation, both 3H-PAC and 3H-prazocin binding increased significantly in young grafts. In aged adrenergically denervated grafts, alpha 2-receptor binding was again significantly reduced whereas alpha 1-receptor binding was not significantly different from that in young denervated grafts. Taken together, these results indicate a selective age-related reduction in hippocampal postsynaptic alpha 2-receptors which is intrinsically determined.

Adrenergic alpha-Agonists↗

PubMedDate not supplied

Hyperactivity and instrumental learning deficits in methylazoxymethanol-treated rat offspring.

Several changes of spontaneous motor and learned behaviours were obtained in the male offspring of pregnant rats that were treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg). MAM-treated offspring, when tested at adult ages, showed notable increases in motor activity parameters as measured by direct observation or in automated photocell test cages. This hyperactive state was accompanied by clear impairments by MAM offspring in the acquisition of instrumental learning in a radial arm maze and in a circular swim maze. In Skinner boxes, MAM offspring made fewer responses during the Fixed Ratio (FR) 1 schedule but did not differ from the saline offspring in the acquisition of the difficult differential-reinforcement-of-low-rates (DRL) 72 sec task. Neurochemical assays indicated that the MAM rats had elevated noradrenaline and dopamine levels in several brain regions. These findings are discussed with regard to possible alterations of habituation processes in MAM rats.

Animals↗

PubMedDate not supplied

Effects of prenatal exposure to tributyltin and trihexyltin on behaviour in rats.

The effects of prenatal administration of tributyltin (1 and 5 mg/kg) and trihexyltin (5 mg/kg) upon the development and behavioural repertoire of rats were studied. The dose levels were selected so as not to induce maternal toxicity. No consistent delay upon occurrence of various maturation markers of the organotin-treated offspring was seen. As adults the tributyltin-treated offspring showed considerable hyperactivity following the initial habituation whereas the trihexyltin-treated offspring showed hyperactivity to a lesser degree. In the spatial learning tasks applied, the radial arm maze and the circular swim maze, tributyltin-treated rats demonstrated a clearly retarded aquisition of the radial arm maze task whereas trihexyltin-treated rats performed as well as the control rats; no differences were obtained in the swim maze task. The tributyltin-treated offspring showed a drastic potentiation of d-amphetamine-induced hyperactivity, whereas trihexyltin treatment induced only a marginal increase.

Animals↗

PubMedDate not supplied

Low-level cadmium exposure of lactating rats causes alterations in brain serotonin levels in the offspring.

Effects on monoaminergic and cholinergic transmitter systems as well as neurotrophins were characterized in developing Sprague-Dawley rats directly exposed to 5 ppm cadmium in the drinking water or indirectly via exposed dams. Cadmium was given to dams during the lactation period, from parturition to postnatal day 17, and/or to the offspring until postnatal day 42. Cresyl violet staining and glial fibrillary acidic protein immunohistochemistry did not reveal any obvious neuropathology after cadmium exposure. Following high-power microwave fixation, concentrations of acetylcholine (ACh) and monoamines were determined in cerebral cortex, striatum, and hippocampus using HPLC with electro-chemical detection. ACh, dopamine, and noradrenaline levels were not significantly affected after the different cadmium exposures. Cortical levels of serotonin were significantly reduced in rats exposed to cadmium during lactation as well as in rats exposed to cadmium during both lactation and postweaning. A major decrease in 5-hydroxyindoleacetic acid was found in cortex and hippocampus in rats exposed to cadmium during lactation. The regional characteristics of cadmium toxicity as reflected in changes of neurotrophins were studied using in situ hybridization histochemistry with oligonucleotide probes and phosphoimaging evaluation. No significant changes in the mRNA expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3, and the high-affinity tyrosine kinase receptor of BDNF, trkB, were detected. The present results demonstrate that exposure to levels of cadmium as low as 5 ppm in the drinking water leads to neurochemical disturbances of the serotonergic system in the offspring during the lactational period.

Acetylcholine↗

PubMedDate not supplied

The effect of citric acid on the availability of tetracyclines in calves.

The effect of citric acid on the availability of tetracyclines was studied in calves. Citric acid did not significantly increase the serum levels of tetracyclines when calves were fed low doses (6-8 mg/kg) of oxytetracycline and chlortetracycline. When the dose of chlortetracycline was increased to 50 mg/kg, addition of citric acid caused higher serum levels the first two hours after feeding. The ratio citric acid: tetracyclines was 5:1 and 25:1. The palatability of the milk replacer was reduced when large amounts of citric acid was added.

Animal Feed↗

PubMedDate not supplied

The erythrocyte uptake of 75Se as an indicator of selenium status in lambs.

The glutathione peroxidase activity (GSH-Px) and the in vitro erythrocyte uptake of 75Se (ESeU) was followed in blood samples from 31 lambs for 105 days. The lambs were divided into three groups; untreated (group U), vitamin E treated (group E) and selenium treated (group Se). The animals in group E were administered intramuscularly 250 mg vitamin E at two weeks interval and those in group Se 0.1 mg Se/kg as sodium selenite monthly. None of the lambs exhibited symptoms of muscular degeneration or any other disease during the trial. Vitamin E had no effect neither on the GSH-Px nor on the ESeU. Thirty days and later after the first Se treatment the GSH-Px was significantly higher in group Se than in the other two groups, but the most rapid increase of GSH-Px in this group was noticed after 44 days. On day 51 a significant decrease of GSH-Px was shown in groups U and E compared with day O. The lambs in groups U and E had significantly higher ESeU on day 36 and later compared with day 0. The administration of selenium in the mineral supplement (10 mg Se/kg) to the lambs in group U and E during the 26 latest days of the study gave an almost significant increase of GSH-Px and a decrease of ESeU. Our experience of the ESeU-test is that it is a simple method, and can be used to evaluate Se status of animals.

Animals↗

PubMedDate not supplied

The availability of tetracyclines in calves.

The bioavailability of oxytetracycline (OTC) and chlortetracycline (CTC) was studied in non-fasting calves. The availability of OTC was found to be 5% and of CTC 37% after oral administration of 10 mg/kg. The availability was reduced when the drugs were given in a milk replacer or in cow's milk. The area under curve (AUC) was reduced 68% when OTC was given in milk replacer, the reduction of CTC availability was 40%. In milk the reduction was 72% for OTC and 47% for CTC. Calcium and iron caused a dramatic reduction of the serum levels. OTC was stored mixed in milk powder at room temperature for 6 months without loss in availability. OTC did not chelate calcium ions in serum. The conclusion drawn from the results was that CTC is more suitable than OTC for oral therapy in calves.

Administration, Oral↗

PubMedDate not supplied

Effects of nefiracetam (DM-9384), a pyrrolidone derivative, on brain monoamine systems.

The pyrrolidone cyclic gamma-aminobutyric acid (GABA) derivative nefiracetam [DM-9384; N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide] has been shown to enhance acquisition and ameliorate amnesia in different learning tasks in rodents. In the present study, the effects of nefiracetam on the brain monoamine systems were studied. Male, adult Sprague-Dawley rats were treated with nefiracetam in single doses (0, 1, 3, 10, 30 or 100 mg/kg, p.o.) and analyzed after 1 and 4 hr, or treated by daily doses (0, 1, 3, 10 or 30 mg/kg, p.o.) for 2 weeks. In general, no or only weak effects were observed on tissue monoamine levels, either following acute or 14 days treatment with nefiracetam. Acute administration of intermediate doses of nefiracetam induced minor increases in dopamine (DA) and homovanillic acid (HVA) tissue levels in the striatum, while hypothalamic 3,4-dihydroxyphenylacetic acid (DOPAC) decreased at 1 hr. Noradrenaline (NA) and serotonin (5-HT) levels increased in some regions after higher doses of nefiracetam. Increases in 5-hydroxyindoleacetic acid (5-HIAA) were also seen at 4 hr, but only after the 3 mg/kg dose. Minor decreases of HVA and DOPAC levels were seen in some regions after treatment with various doses of nefiracetam for 14 days, while an increase in 5-HT levels was observed occasionally. Using in vivo microdialysis in freely moving animals, no significant effects on extracellular levels of HVA, DOPAC and 5-HIAA in the striatum or of HVA, DOPAC and NA levels in the dorsal hippocampus were seen after acute administration of nefiracetam. On the other hand, extracellular hippocampal 5-HIAA levels decreased by 20% after the 1 and 3 mg/kg doses. Nefiracetam, in a concentration range of 1 nM to 10 microM, did not affect the in vitro synaptosomal uptake of [3H]NA and [3H]5-HT in the cortex or of [3H]DA in the striatum. Taken together, nefiracetam appears to exert minor, regionally restricted and not dose-dependent effects on the monoamine systems following either acute or repeated administrations in normal rats. A direct or indirect, possible GABA-mediated, influence of nefiracetam may underlie the modest changes seen on monoamines. The cognitive-enhancing action of nefiracetam does not seem to be related to effects on presynaptic monoamine functions.

3,4-Dihydroxyphenylacetic Acid↗