Genotoxicity of aniline derivatives in various short-term tests

Various substituted aniline derivatives were tested for genotoxicity in several short-term tests in order to examine the hypothesis that a substitution at both ortho positions (2,6-disubstitution) could prevent genotoxicity due to steric hindrance of an enzymatic activation to electrophilic intermediates. In the Salmonella/microsome assay, 2,6-dialkylsubstituted anilines and 2,4,6-trimethylaniline (2,4,6-TMA) were weakly mutagenic in strain TA100 when 20% S9 mix was used, although effects were small compared to those of 2,4-dimethylaniline and 2,4,5-trimethylaniline (2,4,5-TMA). In Drosophila melanogaster, however, 2,4,6-TMA and 2,4,6-trichloroaniline (TCA) were mutagenic in the wing spot test at 2-3 times lower doses than 2,4,5-TMA. In the 6-thioguanine resistance test in cultured fibroblasts, 2,4,6-TMA was again mutagenic at lower doses than 2,4,5-TMA. Two methylene-bis-aniline derivatives were also tested with the above methods: 4,4'-methylene-bis-(2-chloroaniline) (MOCA) was moderately genotoxic in all 3 test systems whereas 4,4'-methylene-bis-(2-ethyl-6-methylaniline) (MMEA) showed no genotoxicity at all. DNA binding studies in rats, however, revealed that both MOCA and MMEA produced DNA adducts in the liver at levels typically found for moderately strong genotoxic carcinogens. These results indicate that the predictive value of the in vitro test systems and particularly the Salmonella/microsome assay is inadequate to detect genotoxicity in aromatic amines. Genotoxicity seems to be a general property of aniline derivatives and does not seem to be greatly influenced by substitution at both ortho positions.     

RNA synthesis in different regions of rat brain at various time intervals after cerebellectomy

RNA synthesis was studied in cerebral cortex, thalamus and brain stem of rat, on the 3rd, 8th, 30th and 75th day after cerebellectomy. An increased RNA synthesis was detected in thalamus at the 30th day and in cerebral cortex and brain stem at the 75th day after cerebellectomy. Our findings suggest that motor compensation following the cerebellectomy could be supported by a spatio-temporal organization of macromolecular synthesis in different brain regions.     

Vasopressin analogues and spatial short-term memory in rats

The effect of vasopressin analogues on short-term memory was tested in the 12-arm radial maze. After the first 6 choices rats (n=6) were removed from the apparatus and allowed to complete the remaining 6 choices 20 min later. Whereas desgly-NH₂-VP, AVP, dAVP and DAVP (3.0 μ/kg) administered 40 min before or immediately after the first 6 choices did not change the incidence of errors in the second series of choices (2.0 errors under control conditions), similarly applied dDAVP deteriorated the rat's performance almost to the chance level of 3 errors. The significance of short-term memory tests for assessing the mnestic role of peptide hormones is stressed.     

Features of the formation and dynamics of short-term image memory in the rat

Direct and indirect methods of delayed reactions showed that short-term image memory of rats elaborated on the basis of conditioned signals in poorly developed and its duration is not more than 1 s. While testing this memory, changes in the behaviour were seen, pointing to the development of "hard state" in the higher nervous activity of animals. Short-term image memory based on complex perception was shown to be well developed in rats, and by many characteristics it approximated to the memory of highly organized animals. The ability to reproduce the short-term image memory on the basis of conditioned signals is supposed to be a complex form of psychonervous activity of animals, and in rodents it appears to be at an initial stage of development.     

A non-taste cue of sucrose in short-term taste tests in rats

Data are presented showing that rats can discriminate amongsucrose solution concentrations by some cue other than taste,possibly by olfaction. Non-taste factors need to be consideredin taste discrimination studies.     

Changes in HPA reactivity and noradrenergic functions regulate spatial memory impairments at delayed time intervals following cerebral ischemia

This study investigates the association of ischemia-induced spatial memory impairment to alterations of the HPA axis and noradrenergic activation post insult. Experiment 1 characterized the effects of 10 min forebrain ischemia on corticosterone (CORT) secretion following ischemia and in response to spatial memory assessment in the Barnes maze, as well as the impact of pre-ischemia treatment with the glucocorticoid inhibitor metyrapone (175 mg/kg; s.c.). The results showed that cerebral ischemia represents a significant physiological stressor that upregulated CORT secretion 1, 24 and 72 h post-ischemia but not at 7 days. In response to testing in the Barnes maze ischemic animals showed elevated CORT secretion simultaneously with spatial memory deficits. The single dose of metyrapone attenuated the ischemia-induced adrenocortical hyper-responsiveness and subsequent memory deficits despite not providing neuroprotection in the hippocampal CA1 pyramidal cells. To complement these findings, we examined whether norepinephrine which provides positive feedback to the HPA axis and is upregulated following brain ischemia could influence memory performance at delayed intervals after ischemia. Experiment 2 demonstrated that pre-testing administration of the alpha2-adrenoceptor agonist clonidine (.04 mg/kg, s.c.) attenuated ischemia-induced working memory impairments in a radial maze while opposite effects were obtained with the antagonist yohimbine (.3 mg/kg, s.c.). Post-testing administration of clonidine produced spatial reference memory impairments in ischemic rats. The findings from the current study demonstrate increased sensitization and responsiveness of systems regulating stress hormones at long intervals post ischemia. Importantly, we demonstrate that these effects contribute to post ischemic cognitive impairments which can be attenuated pharmacologically even in the presence of hippocampal degeneration at time of testing.     

Influence of partial intraspecies deprivation on short-term image-driven memory in rats

Behavior and short-term memory function were studied in adult rats risen under conditions of partial intraspecies social deprivation. Testing of delayed responses (and emotional state) showed that the partial deprivation of intraspecies communication at the early stage of postnatal ontogeny led not only to disorders of short-term memory in the adult rats, but also to behavioral alterations, which may be due to impaired development of the regulatory mechanisms of motivation and emotions.     

The perception of empty and filled time intervals by rats

In experiment 1, rats were trained in a within-subjects design to discriminate durations of a filled interval, and durations of an empty interval (an unfilled interval marked at the beginning and end by a 500 ms tone). Training and psychophysical testing was conducted with three sets of anchor durations. Rats made more long responses for filled than for empty intervals at signal durations greater than the geometric mean. In experiment 2, group same was trained similarly to the rats in experiment 1 with the ambient conditions (houselight illumination) remaining the same during the inter-trial interval and the empty intervals. Group different was trained with the houselight turned off during empty and filled intervals. The similarity of ambient conditions during the inter-trial interval and the empty intervals did not significantly affect timing. Filled intervals were timed more precisely and they were perceived as longer than empty intervals of the same duration. The psychophysical functions superimposed across anchor duration sets. These results are the first clear evidence of a filled interval illusion in rats, and they suggest that this difference may reflect a clock rate effect (greater for filled intervals) rather than a switch latency effect (slower for empty intervals).