Nina Harris

Effect of Arginine Administration on Plasma and Brain Levels of Arginine and Various Related Amino Compounds in the Rat

Arginine (ARG) was injected (0.8 g/kg, i.p.) into rats and levels of ARG were determined in plasma and four brain areas in the morning and afternoon. In control rats, brain values for ARG and some amino compounds are lower in the afternoon than in the morning. After ARG administration, ARG levels increase about 10-fold in the plasma and 2- to 3-fold in the brain areas. Brain ARG levels follow plasma levels. Elevated ARG levels affect a number of related amino compounds both in the plasma and all brain areas most notably ornithine, phosphoserine, glycine, GABA and ammonia. An increase of citrulline after ARG administration suggests the possibility of ARG-stimulated nitric oxide formation in the midbrain. Thus, ARG shows a daily rhythm in the plasma and brain and its administration increases ARG brain levels which seem to follow plasma levels. In addition, ARG alters a number of other amino compounds most notably GABA, glycine, ornithine and ammonia, indicating that some pharmacological effects seen after ARG administration might be caused by elevated levels of ARG and/or changes in other amino compounds.

Effects of repeated stress on plasma arginine levels in young and old rats

The effect of age and recurring stress responses on endogenous plasma arginine (ARG) concentrations were determined. Blood from catheterized young (3 months) and old (24 months) were used to ascertain the plasma concentrations of ARG under baseline conditions, during a 30-min immobilization experience and during a 3.5 h poststress period. Rats were again immobilized and blood drawn following a 1 day rest period (day 3) and then after an additional 3 day rest period (day 7). For young animals, ARG levels decrease significantly after 30 min of stress and remain suppressed during the entire poststress period (3.5 h). After a 1 day rest period, these young rats may have exhibited adaptation to stress on day 3. Old animals showed little or no reduction in plasma ARG concentrations during and after immobilization stress exposure on all three occasions. Baseline levels of old animals were lower in comparison to young animals and their stress responses were smaller. Thus, it is possible that significant changes in plasma ARG levels (as the nitric oxide precursor) during or after stress could serve as an indicator of impending pathology such as cardiovascular disease or immunocompetency.

Voluntary alcohol and cocaine consumption in “low” and “high” stress plasma catecholamine responding rats

Alcohol (ethanol) and cocaine preference in a free-choice, two-bottle situation was measured in two groups of male and female low and high plasma catecholamine stress responding rats. Alcohol intake of a 5% solution (percent or mg/kg) showed markedly different but individually consistent intake among animals. High plasma catecholamine stress responders consumed more ethanol than did low responders. A similar finding was made when animals consumed a 10% solution; fluid intake fell but total ethanol intake remained the same. High responders drank more than did low responders. After a period of 4 weeks of water only, animals were reexposed to 5% ethanol and a significant positive correlation was seen in the drinking habits of the animals. Afterwards, exposure to a 0.02% cocaine solution resulted in cocaine intake which varied among animals, but was consistent for an individual rat and did not correlate with alcohol consumption. In general, ethanol and cocaine consumption correlated positively with the plasma catecholamine stress response. No significant differences in drinking habits were observed between the sexes. Thus, alcohol preference is a relatively stable characteristic of an animal, is higher in high as compared to low plasma catecholamine stress responders and does not correlate with voluntary cocaine consumption.

Effects of buspirone on plasma catecholamines, heart rate, and blood pressure in stressed and nonstressed rats

The influence of buspirone upon plasma catecholamine levels, heart rate, and mean arterial blood pressure was studied in stressed and nonstressed rats. Measures were obtained directly via indwelling aortic catheters. Drug or vehicle were given acutely (10 mg/kg, IP) or twice a day for 10 days (10 mg and 20 mg/kg, SC). In nonstressed rats, a single dose of buspirone increased markedly plasma norepinephrine and epinephrine levels and decreased significantly heart rate with no effect on blood pressure. During stress, stress-induced increases in catecholamine levels were further elevated by the drug, whereas stress-induced increases of heart rate and mean arterial blood pressure were reduced. In chronically-pretreated rats, the effects of buspirone were similar to those observed after an acute injection. These effects of buspirone on plasma catecholamines are very different from those seen with other anxiolytics, whereas effects on heart rate and blood pressure are more similar.

Effect of repeated stress on plasma catecholamines and taurine in young and old rats

The effect of age and multiple stress responses on plasma norepinephrine (NE), epinephrine (EPI), and taurine (TAU) levels were determined in F344 rats. Blood samples obtained from catheterized young (3 months) and old (24 months) animals were used to examine plasma levels of NE, EPI, and TAU under baseline conditions and in the same animals after a 30-min immobilization stress. Rats were again immobilized and blood drawn (Day 3) following a 1-day rest period and, after an additional 4-day rest period (Day 7). Age differences seen between young and old rats were not the same for the three neurochemicals measured but were relatively unique for the specific biochemicals. In old animals baseline values of NE but not EPI and TAU were higher then young animals and all three values did not change for the baseline during the two additional stress exposures. Initial stress responses were similar for all three biochemicals in both age groups. Although no signs of adaptation were evident in the old animals, adaptation to immobilization was seen for EPI and TAU but not NE on the third occasion in the young animals. Correlations seen between NE and EPI in young and old rats on the first day disappeared during the second stress period but were again seen during the third stress exposure suggesting subtle indicators of repeated stress subject to adaptation. TAU values for young but not old rats correlated positively with EPI concentrations during the first stress exposure and negatively after the immobilization was terminated indicating a regulatory interaction between EPI and TAU present in young but lost in old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of arginine administration on the levels of arginine, other amino acids and related amino compounds in the plasma, heart, aorta, vena cava, bronchi and pancreas of the rat

Arginine (0.8g/kg, ip) or a vehicle was administered to rats and the levels of arginine and a large number of related amino compounds++ were measured in plasma, heart, aorta, vena cava, pancreas and bronchi at specified time intervals. Arginine levels (nmol/ml) increased in the plasma from 237 to 3172 at 15 min, 1236 at 30 min and 509 at 120 min. Peak concentrations (nmol/g) of arginine are reached in the tissues at 15 or 30 minutes with control and postinjection values of 500 and 1769 in the heart, 314 and 1563 in the aorta, 575 and 2976 in the vena cava, 760 and 1943 in the bronchi, and 234 and 3638 in the pancreas. Arginine injection also affects a number of amino acids and related compounds in the plasma and tissues most notably ornithine, isoleucine, phosphoserine, leucine and ethanolamine. However, plasma level changes do not predict tissue level changes which are highly specific for an individual compound and tissue. There was no general indication that arginine injection stimulates nitric oxide (NO) formation in any tissue. Thus, arginine is rapidly absorbed from the abdominal cavity into the blood stream, is quickly taken up by the tissues studied and disappears after about 2 to 3 hours. The effects seen after arginine administration could be caused by arginine per se and/or changes in one or more of the related amino compounds but not by NO.

Genomic screening for genes predisposing to bipolar disease

Twenty-one multiplex bipolar (BP) families, consisting of 365 informative persons (of whom 153 have BPI, schizoaffective, BPII with major depression or recurrent unipolar diagnoses) were studied in a systematic screening of chromosomes 1, 10q, 11q, 13, 15 and 17 for linkage, using DNA markers. Simulation research has indicated that this pedigree series has greater than 50% power to detect linkage when only 25% of families are linked (1% recombination) to the marker. Two and three-point linkage analysis (using the diagnoses mentioned above as affected and an autosomal dominant disease mode1) did not reveal any evidence for linkage (total lod scores less than - 2) under the hypothesis of homogeneity. Inspection of two-point lod scores by family did not reveal evidence for heterogeneity in nearly all cases. Heterogeneity analyses using the admixture test were conducted for a region of 11q13 (where inspection of 2-point analyses for individual families revealed several weakly positive lod scores) which yielded a maximum lod score of 1.5 when the fraction of linked families was estimated at 25%. These results indicate that a gene responsible for BP disease in a majority of the families studied is unlikely to originate within the chromosomal regions covered by the DNA markers used.

The plasma catecholamine stress response is characteristic for a given animal over a one-year period

The same male and female rats with indwelling jugular catheters were stressed (immobilization) on two occasions at the ages of 3 to 4 and 15 to 16 months. Plasma levels of the catecholamines (CA) norepinephrine (NE) and epinephrine (E) were determined before and during stress at each session. During stress, plasma NE and E levels increased markedly. At the younger age, female animals showed markedly higher CA levels than male animals. After one year, stress CA levels were higher for both sexes, but had increased markedly in male and little in female animals. A positive correlation was found between the plasma CA stress response of individual animals at both sessions; this correlation was stronger for males and NE. This indicates that high responders usually remain high responders, low responders remain low and intermediate responders intermediate. In conclusion, the plasma CA stress response increases markedly in male, but little in female rats over the period of 1 year and the relative magnitude of the individual stress response remains a characteristic of each given animal.

Maudsley reactive and non-reactive rats differ in exploratory behavior but not in learning.

The Maudsley reactive (MR) and Maudsley non-reactive (MNR) inbred rat strains were created as an animal model of anxiety, based on open field behavior. We wished to determine whether previously described characteristic open field behavior and learning deficits in conditioned avoidance could be generalized to other paradigms of exploratory behavior (such as the staircase test) and learning (such as the T-maze swim test). As with other open field paradigms, the MR rats showed stable and large differences in the staircase test, compared with the MNR rats. In contrast, large and stable learning differences in conditioned avoidance and T-maze swim tests were not observed. We conclude that the MR rats exhibit exploratory behavior that is inhibited in a wide variety of paradigms, but learning deficits are not major characteristics of the phenotype. The inhibited exploratory behavior is a stable characteristic with large inter-strain differences, making measures of open field behavior suitable for quantitative trait loci analysis to determine the genes which explain these large and stable strain differences. Identification of these genes could provide clues to the genetic origins of some human anxiety disorders.

Effect of repeated stress on a number of plasma amino acids and related compounds in young and old rats

A number of amino compounds were studied in the plasma of young and old rats exposed to an immobilization stress on 3 different days. Baseline values were similar for all compounds between age groups except for slightly higher phenylalanine levels in old animals. Most differences were seen in the stress responses. Stress response intensities for alanine, aspartic acid, methionine, phenylalanine, and tyrosine were generally higher in old rats and recovery times from stress were usually longer. Although the stress responses decreased in young rats for some compounds over the three exposures, old rats showed no or less adaptation during this time. All the other amino acids showed no marked age effects. This study shows that certain plasma amino acids can serve as selective indicators of biological age and that their stress responses might be better markers of the aging process than their resting levels.