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Biomedical subjects

G L Kramer

Publications and source records attributed to G L Kramer.

52 records · Page 3Linked to original sources
PubMed1994

Previous stress increases in vivo biogenic amine response to swim stress.

In vivo microdialysis was used to determine biogenic amines in medial prefrontal cortex of rats exposed to eight minutes of swim stress on two consecutive days. On the first day of stress, norepinephrine (NE) efflux increased by 183% over baseline after stress, while dopamine (DA) and serotonin (5-HT) remained stable throughout. On the second day of stress, a robust increase was observed in all 3 neurotransmitters measured, with (NE), (DA), and (5-HT) increasing by 310%, 441% and 496% respectively, and remaining elevated for an hour or more after stress. This suggests that the first exposure to swim stress, while not causing dramatic changes in biogenic amine release, may sensitize biogenic amines in medial prefrontal cortex to subsequent swim stress. Our results also serve as preliminary data concerning the neurochemical changes which might underlie the forced swimming model of "behavioral despair".

Animals↗
PubMed1993

Intravenous sodium lactate decreases plasma GABA levels in man.

Gamma aminobutyric acid (GABA), an inhibitory neurotransmitter, may play an important role in anxiety. We studied changes in plasma GABA levels in nine healthy subjects before and after infusions of sodium lactate and dextrose. Plasma GABA significantly decreased during infusions of sodium lactate (109.3 +/- 4.4 versus 91.6 +/- 5.1 pmol/ml; P = 0.0001) but not during infusions of dextrose.

Adult↗
PubMed1993

Desipramine does not alter plasma GABA in patients with major depression.

Low plasma GABA is a biological marker for depression in a subset of patients tested. Plasma GABA has been shown to reflect brain GABA activity. This marker has many characteristics of a trait marker for depression, including stability with time, and lack of influence by coincident factors such as gender, season, time, activity or diet. We here report that plasma GABA remained stable after 4 weeks of treatment with desipramine in patients with major depression. Since the levels of plasma GABA did not change with time, nor with clinical improvement, plasma GABA is not a state marker of depression.

Adult↗
PubMed1993

Low plasma GABA is a trait-like marker for bipolar illness.

Plasma gamma-aminobutyric acid (pGABA) is an index of brain GABA activity and a peripheral marker of mood disorder. Previous research has indicated that pGABA is abnormally low in approximately 40% of patients symptomatic with primary unipolar depression. We have now measured pGABA in a series of patients with bipolar disorder. Blood samples for GABA determinations were collected soon after admission to hospital or clinic while patients were symptomatic. In both manic and depressed phase bipolar patients, mean levels of pGABA were significantly lower than in healthy control subjects. The distribution of pGABA in bipolar patients, whether manic or depressed, was similar to that in symptomatic unipolar depression, with 30% to 40% having pGABA levels lower than the control range. These data indicate that low pGABA is not specific to the depressed state, as it is also found in the manic phase of bipolar disorder. Low pGABA may represent a shared biologic correlate between bipolar and unipolar illness.

Adult↗
PubMed1992

Low plasma gamma-aminobutyric acid levels in male patients with depression.

Plasma levels of gamma-aminobutyric acid (GABA) were significantly lower in males with primary unipolar major depressive disorder than in healthy controls. Although the difference in means between control and symptomatic depressed patient groups was small, the distribution of plasma GABA in the depressed patients was markedly different from controls. Forty percent of depressed patients had plasma GABA levels below those of controls. Plasma GABA levels correlated positively with duration of illness, and negatively with age at onset of the mood disorder and the total Endogenomorphic Symptom Score on the Hamilton Rating Scale. Plasma GABA levels may be a biochemical marker of vulnerability to depression, as opposed to a consequence of the illness. A low GABA condition in depression fits and complements the prevailing biogenic amine hypotheses of depression.

Adult↗
PubMed1992

Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls.

The acute effects of diazepam on plasma GABA were determined in 18 patients with panic disorder, 13 patients with generalized anxiety disorder and 20 healthy controls. All subjects were benzodiazepine-naive. Four logarithmically increasing doses of diazepam/placebo were administered intravenously at 15-min intervals on 2 separate days. Plasma GABA was measured at baseline and 3 min after the highest dose of diazepam/placebo. There was an overall decrease in plasma GABA that was significantly greater following diazepam compared with placebo, but no group differences in response. In a separate group of 18 panic disorder patients receiving chronic benzodiazepine treatment with alprazolam, the same diazepam infusion procedure (no placebo day) produced decreases in plasma GABA similar to those seen in the untreated panic disorder patients. The clinical and physiologic implications of these findings are discussed.

Adult↗
PubMed1990

Plasma GABA in mood disorders.

Plasma levels of gamma-aminobutyric acid (GABA) were determined in 68 healthy controls and in 133 patients with mood disorder. Plasma GABA levels were significantly lower in the patients with mood disorder compared to controls. Levels of plasma GABA were similar among diagnostic groups (primary unipolar depression, bipolar depression, mania, and secondary depression). No differences in plasma GABA were found in patients classified according to family history, nor were any correlations found between plasma GABA levels and severity of depression as determined by the 17-item Hamilton Rating Scale for Depression. These findings support the notion that low plasma GABA may represent a biological marker for mood disorder.

Affective Disorders, Psychotic↗
PubMed1981

Inhibition of separated forms of cyclic nucleotide phosphodiesterase from pig coronary arteries by 1,3-disubstituted and 1,3,8-trisubstituted xanthines.

A series of xanthines with varied substituents in the 1, 3, and 8 positions were prepared in an attempt to understand the structure--activity relationship for alkylxanthines as inhibitors of two different forms of cyclic nucleotide phosphodiesterase. Polar substituents on the 1 or 3 position of the xanthine reduced the potency of the xanthines to inhibit both the calmodulin-sensitive and the "cyclic AMP specific" forms of phosphodiesterase. Polar substituents on the 8 position of the xanthine, other than a carboxylic acid, increased the potency to inhibit the calmodulin-sensitive form of phosphodiesterase, if they were capable of donating electrons to the xanthine nucleus. On the other hand, any substituent in the 8 position larger than H reduced the potency of the xanthines to inhibit the cyclic AMP specific form of phosphodiesterase. Topographical maps of the active sites of the two forms of phosphodiesterase are presented in summary.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Inhibition of separated forms of phosphodiesterases from pig coronary arteries by uracils and by 7-substituted derivatives of 1-methyl-3-isobutylxanthine.

A series of 7-substituted 1-methyl-3-isobutylxanthines was designed in an attempt to increade the specificity of the 1-methyl-3-isobutylxanthine (MIX) structure for one of the two cyclic nucleotide phosphodiesterase peaks isolated by DEAE-cellulose chromatography of the soluble fraction of the intima + media layer of pig coronary arteries. A series of 1,3-dialkyluracils was of low potency as inhibitors of either peak I or peak II. The 7-substituted xanthines were prepared by alkylation of MIX with the corresponding alkyl or aralkyl halide in DMF containing K2CO3. These compounds were, in general, much less potent inhibitors of peak II activity than was MIX, but some of them retained the potency of MIX as inhibitors of peak I and, therefore, were relatively specific for inhibition of peak I. 7-Bzl-MIX was the most selective compound tested; it was a potent inhibitor of peak I activity but was much less effective as an inhibitor of peak II activity. Substitution of either electron-withdrawing (nitro) or electron-donating (methoxy) groups on the 7-benzyl moiety reduced the effectiveness of the 7-benzyl compounds as inhibitors of peak I. Chlorobenzyl substitution increased the potency slightly over the benzyl but not the selectivity between peaks.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

Beta-adrenergic receptor changes in learned helplessness may depend on stress and test parameters.

Behavioral deficits following inescapable stress (learned helplessness) may serve as an animal model of depression. Previous studies using foot-shock stress to induce learned helplessness and a bar-press test for the stress-induced behavioral deficit have found increased beta-adrenergic receptor density in the hippocampus of learned helpless rats. We replicated these experiments using a tail-shock stress and the shuttle-box test. In our experiments, rats that developed learned helplessness after inescapable stress did not demonstrate any significant differences in beta-adrenergic receptor density or affinity in the frontal cortex, cerebellum, or hippocampus compared to the nonhelpless rats, nor to the tested control rats. These results suggest that beta-adrenergic receptor changes in learned helplessness may depend on the specific stress and test procedures used.

Animals↗
PubMedDate not supplied

Serotonin and learned helplessness: a regional study of 5-HT1A, 5-HT2A receptors and the serotonin transport site in rat brain.

Serotonin (5-HT) plays a central role in the neurochemistry of the learned helplessness animal model of depression. Using quantitative autoradiography, we measured the density of 5-HT1A and 5-HT2A receptors and of 5-HT transport sites in medial prefrontal cortex, dorsal hippocampus, septum, hypothalamus, and amygdala in learned helpless rats, and in rats that were nonhelpless after inescapable stress, as well as in shuttlebox-tested and nonhandled controls. We found no changes in 5-HT1A receptor density among the groups in any region studied. In dorsal hippocampus, 5-HT2A receptor density was decreased in nonhelpless rats, while in amygdala 5-HT2A receptor density was decreased in both groups of stressed rats, whether helpless or nonhelpless. In the hypothalamus 5-HT2A receptor density, was decreased in helpless rats as compared to controls. In medial prefrontal cortex, the serotonin transport sites showed decreased density in helpless rats as compared to controls but not to nonhelpless rats. These findings further highlight the complexity of regional 5-HT effects in the learned helplessness animal model.

8-Hydroxy-2-(di-n-propylamino)tetralin↗