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Biomedical subjects

K Schlesinger

Publications and source records attributed to K Schlesinger.

At least 19 recordsLinked to original sources
PubMed1992

Interaction of the erythroid transcription factor cGATA-1 with a critical auto-regulatory element.

We have performed a mutational analysis of the promoter for the chicken erythroid-specific GATA-1 transcription factor, and have investigated in detail the interaction of the factor with an upstream auto-regulatory element (ARE). We find that a single proximal GATA binding site of the ARE is required for promoter activity in primary erythroid cells; however, this minimal promoter is inappropriately active in fibroblasts. At least two molecules of GATA-1 can interact with the ARE, and sequences outside of the consensus site appear critical for the transcriptional activity of the bound protein. Finally, we provide evidence for complex protein/DNA interactions at the ARE, including the ability of GATA-1 to bend DNA.

Animals↗
PubMed1989

Behavioral and reproductive differences in mice as a function of inbreeding.

Twenty brother-sister pairs of mice were randomly selected from a genetically heterogeneous population of mice to begin a schedule of inbreeding that lasted for six generations (F = 0 to F = .732). We examined a number of indices of reproductive behavior and found that all declined as a function of inbreeding. Specifically, there was a consistent decline in the number of fertile matings, in the number of offspring that survived to weaning, and in the weight of the pups at the time of weaning (21 days of age). We also examined a number of behaviors with the following results: there was a systematic increase in the number of trials required to learn an active avoidance task and a consistent decrease in the number of trials required to extinguish this habit. We observed a statistically significant difference in the retention of a passive avoidance habit, but these results were quite variable and not consistent across generations of inbreeding. Finally, we observed that inbreeding had little effect on measures of locomotor behavior.

Animals↗
PubMed1988

Nigral 5-HT and substance P-induced enhancement of passive avoidance retention.

Peripheral, posttraining injection of substance P (SP) has been shown to facilitate the retention of aversive and appetitive learning tasks, suggesting that SP may play a role in information processing. In addition, SP may modulate the release of nigrostriatal monoamines, which have also been linked with avoidance learning. This paper examines the interaction between SP and nigrostriatal monoamines by observing the behavioral effects of neurochemical lesions on SP-induced avoidance retention, and by measuring changes in nigrostriatal monoamine activity and receptor regulation following avoidance training and SP injection. In Expt. 1, 5,7-dihydroxytryptamine lesions of the substantia nigra, but not the caudate, attenuated the retention-enhancing effects of posttraining SP injection. Further, 6-hydroxydopamine lesions of the substantia nigra produced a deficit in avoidance conditioning that was reversed by posttraining SP injection. Expts. 2 and 3 demonstrated that although passive avoidance training and posttraining SP injections did not significantly alter nigral 5-hydroxytryptamine (5-HT) activity, SP increased 5-HT1 receptor density. It was concluded that SP may affect avoidance retention by modulating nigral 5-HT activity.

Animals↗
PubMed1986

The effect of substance P and its fragments on passive avoidance retention and brain monoamine activity.

It has been shown that substance P(SP), as well as its carboxy and amino terminal fragments, affects a wide range of behaviors. In order to test the CNS activity of these fragments, we measured their effects on passive avoidance learning and monoamine activity. Following one-trial passive avoidance training, mice were injected intraventricularly with either a carboxy or amino terminal SP fragment (SP-C or SP-N), SP itself or phosphate-buffered saline (PBS). SP-N enhanced avoidance retention, which was tested 24 h after training. In a second experiment, monoamine activity was measured one hour after intraventricular injection of SP, PBS or SP fragments. SP-C decreased both nigral 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) and, to a lesser extent, 3,4-dihydroxyphenylacetic acid/dopamine, while SP-N increased nigral 5-HIAA/5-HT. It was concluded that SP-N and SP-C can exert behavioral and neurochemical effects that may be independent of the parent SP molecule.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Substance P facilitation of memory: effects in an appetitively motivated learning task.

Food deprived, heterogeneous strain (HS/IBG) mice were trained on two different discrimination tasks for food reinforcement. In one experiment animals were trained to make spatial discriminations in a T maze. Immediately after training they were given subcutaneous injections of either substance P (1 ng/g) or vehicle. Twenty-four hours later the animals were given reversal training in the same maze. The results showed that substance P-treated animals took significantly longer to acquire the reversal habit than did control mice. In a second experiment, animals were trained to make visual discriminations in a T maze. Immediately after reaching acquisition criterion animals were injected with either substance P (1 ng/g) or vehicle. Different groups of mice were retrained on the same task either 1, 2, 3, or 7 days after original learning. Savings scores were calculated and, at every interval, substance P-treated mice retained the task better than control animals. One interpretation of these data is that substance P-treated mice remembered the original task significantly better than vehicle-injected control animals.

Adrenocorticotropic Hormone↗
PubMed1985

Nicotine-produced relearning deficit in C57BL/6J and DBA/2J mice.

Acute nicotine administration has been shown to influence the acquisition and retention of learning tasks. In order to investigate the many possible behavioral and pharmacological effects of nicotine, a modified 2 X 2 state-dependent learning design was used to assess nicotine's effects on active avoidance learning. Male and female mice of the C57BL/6J (C57) and DBA/2J (DBA) inbred strains were injected with a control solution or with 0.5, 1.0, or 2.0 mg/kg nicotine 5 min before the start of training and, following a 24-h period, 5 min before retraining. Nicotine had no effect on the acquisition of the learning task but, depending on strain and sex, did have an effect on relearning. Relearning in the C57 males was unaffected by nicotine injection, whereas the most prominent effect of nicotine in the C57 females and the DBA males and females was a retrieval deficit. The prevalence of a nicotine-induced retrieval deficit in the present experiment suggests that those mechanisms underlying the retrieval of previously learned information are, in part, mediated or modulated by perturbations within nicotine-sensitive areas of the central nervous system.

Animals↗
PubMed1983

Substance P enhancement of passive and active avoidance conditioning in mice.

In a series of seven experiments we explored the effects of peripherally administered substance P on passive and active avoidance conditioning in mice of two genotypes. The peripheral post-trial administration of substance P significantly enhanced the retention of a single-trial passive avoidance task. This effect was dose dependent; 1 ng/g of substance P enhanced the retention of this habit, whereas higher and lower doses were either less effective or ineffective. In heterogeneous strain (HS) mice, substance P administered before training on an active avoidance task did not alter the rate at which these animals learned this habit. However, animals that had been trained with substance P were significantly more resistant to extinction than were animals that had been injected with vehicle. Similarly, C57Bl/6J mice that had been treated with substance P immediately after active avoidance training were more resistant to extinction than were mice that had been given control injections. The enhancement of retention of the passive avoidance habit with substance P was reversed in animals that had been pretreated with naltrexone. Substance P enhancement of the retention of the passive avoidance habit, and its reversal with naltrexone, was observed in both sham operated and adrenalectomized mice.

Animals↗
PubMed1983

Substance p reversal of electroconvulsive shock and cycloheximide-induced retrograde amnesia.

Subcutaneous post-trial administration of the neuropeptide substance P was found to reverse the amnestic effects of both electroconvulsive shock and cycloheximide. Substance P was observed to reverse the amnestic effects of cycloheximide in both C57B1/6J and heterogeneous strain (HS) mice. Substance P was found to reverse the amnestic effects of electroconvulsive seizures in C57B1/6J animals. Peripheral injections of substance P were also found to facilitate the retention of a single-trial passive avoidance habit in animals of both genotypes, provided a weak footshock was used during training.

Animals↗
PubMed1979

Relations between nicotine-induced convulsive behavior and blood and brain levels of nicotine as a function of sex and age in two inbred strains of mice.

Nicotine levels in blood and whole brain were measured as a function of sex and age in C57BL/6J and DBA/2J mice and compared to the behavioral responses following an intraperitoneal injection of nicotine. The results indicate that blood levels of nicotine alone do not accurately predict either brain levels of nicotine or the behavioral responses to a single injection of nicotine. In general, brain levels of nicotine proved to be a fairly accurate predictor of the behavioral responses to nicotine. The data indicate that the sexes differ in their sensitivity to nicotine. Forty-two-day-old male mice of both strains given comparable doses of nicotine were found to concentrate the drug in the brain more than females. However, there was no corresponding increase in sensitivity to this increased brain concentration as measured by LD50, ED50, latency to tremor or latency to death.

Aging↗
PubMed1976

Developmental patterns of seizure susceptibility in inbred strains of mice.

Samples of mice from each of 6 inbred strains were tested for audiogenic and electroconvulsive seizures at 5 ages (14, 21, 28, 35, and 42 days). A moderately large within-strain correlation (.67) was found, indicating that developmental patterns of susceptibility to audiogenic and electroconvulsive seizures are similar within each strain. The finding of an even larger between-strain correlation (.91) indicated that strains which are highly susceptible to audiogenic seizures are also likely to be highly susceptible to electroconvulsive seizures. In a 2nd experiment, whole brain norepinephrine and serotonin were assayed in each of 5 inbred strains at 21 and 42 days of age. Results were consistent with the hypothesis that levels of these amines are inversely related to seizure susceptibility. Mice from strains which were susceptible to seizures at 21 days of age had significantly lower levels of norepinephrine and serotonin in brain than did 42-day-old, seizure-resistant animals.

Acoustic Stimulation↗
PubMed1976

Selective breeding for acoustic priming.

Data on eight generations of selective breeding for acoustic priming efficacy are reported. The realized heritability of this trait is approximately 0.2-0.3, indicating that the trait is determined in part by genetic factors. Animals selectively bred for acoustic priming do not differ in terms of first-trial (i.e., non-priming-induced) audiogenic seizures. These data suggest that acoustic priming and first-trial audiogenic seizures are controlled by different genetic mechanisms.

Acoustic Stimulation↗
PubMed1976

Prevention of memory loss following puromycin treatment.

Female C57BL/6J mice were trained on a one trial passive avoidance response. Twenty-four hours later, they were treated with puromycin in combination with either 2.0 or 10.0 mg/kg of amphetamine, 0.3 mg/kg of strychnine, or 20.0 or 50.0 mg/kg of pentylenetetrazol. Tests one week after training revealed that treatment with these stimulant drugs prevented the memory loss characteristic of puromycin; an exception being those animals injected with the low dose of amphetamine. Biochemical determination of amino acid incorporation into protein revealed that none of the stimulant drugs used significantly altered the extent or the duration of protein synthesis inhibition induced by puromycin. These results are interpreted as showing that the amnesic effects of puromycin can be counteracted by a state of heightened nervous system excitation.

Animals↗
PubMed1976

Inhibition of acoustic priming in mice.

Mice of the C57BL/6J strain can be made susceptible to audiogenic seizures by a process known as acoustic priming. Acoustic priming can be blocked when the animals are injected either with puromycin or with puromycin aminonucleoside before the application of the priming stimulus. Cycloheximide, diphenylhydantoin, and d-amphetamine had little effect on priming-induced audiogenic seizures in these animals. All of these drugs, however, when given in combination with puromycin reversed in the protective action of puromycin against audiogenic seizures. Puromycin administered to 19-day-old mice increased susceptibility to electroconvulsive seizures when the animals were tested at 22 days of age. It is suggested that puromycin is able to block priming-induced audiogenic seizures by producing abnormal electrical activity in the brain or through an interference with normal neurohumoral transmission by incomplete peptides.

Acoustic Stimulation↗
PubMed1975

Levels of pyridoxine and susceptibility to electroconvulsive and audiogenic seizures.

The effects of pyridoxine deficiency and the administration of supplemental vitamin B6 on audiogenic and electroconvulsive seizures were studied in two inbred strains of mice and their F1 hybrids. Pyridoxine deficient diets increased seizure risk, whereas supplemental vitamin B6 protected these animals against seizures. Penicillamine and thiosemicarbazide, at doses which lowered brain levels of pyridoxine by only 10%, increased seizure risk. Diets deficient in zinc and copper did not alter susceptibility to either audiogenic or electroconvulsive seizures. DBA/2J mice, genetically susceptible to audiogenic seizures, have the same endogenous levels of pyridoxine in the brain as do C57Bl/6J mice, which are resistant to audiogenic seizures.

Acoustic Stimulation↗
PubMed1975

Catechol-O-methyl transferase and monoamine oxidase activities in brains of mice susceptible and resistant to audiogenic seizures.

The activities of catechol-O-methyl transferase (COMT), monoamine oxidase (MAO), and a methanol forming enzyme were studied in whole brain homogenates and in livers obtained from DBA/2J, C57B1/6J, and F1 hybrid mice. DBA/2J mice are extremely susceptible to audiogenic seizures, whereas C57B1/6J mice are resistant to sound-induced convulsions. C57B1/6J mice were found to have significantly higher brain levels of COMT, while MAO activities were not different in animals of these genotypes. No methanol forming activity was detected in animals of either strain. No differences were found in hepatic activities of either COMT or MAO. Pyrogallol was shown to protect DBA/2J animals against audiogenic seizures.

Acoustic Stimulation↗