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Biomedical subjects

K A Roth

Publications and source records attributed to K A Roth.

124 records · Page 7Linked to original sources

Central and peripheral contributions to hypothalamic epinephrine.

Hypothalamic epinephrine concentrations were examined following adrenal demedullation or after surgical hemisection of ascending projections to the hypothalamus. Following surgical transection epinephrine in the ipsilateral hypothalamus was depleted by approximately 60%. Adrenal demedullation had no effect on hypothalamic epinephrine concentrations. It was concluded that hypothalamic epinephrine was central in origin.

Adrenal Medulla↗

In vivo intraneuronal MAO inhibition in rat brain SKF 64139, comparison to other potent PNMT inhibitors.

SKF 64139, a potent inhibitor of adrenal and brain phenylethanolamine-N-methyltransferase (PNMT), was found to have effects on catecholamines, serotonin and their metabolites in rat brain which suggest it may act as a potent inhibitor of monoamine oxidase (MAO) 'in vivo' after acute administration. Evidence of this was obtained by observing the concurrent elevation of serotonin and depletion of its major metabolite 5-hydroxyindoleacetic acid (5-HIAA), as well as depletion of the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenyl-acetic acid (DOPAC) following acute administration. Additional evidence was obtained by antagonism of the increase in acid metabolites and depletion of amines following treatment with reserpine. Using the depletion of brain DOPAC as an index of MAO activity, an ED50 of 3-4 mg/kg was found for SKF 64139 as an "in vivo' MAO inhibitor.

3,4-Dihydroxyphenylacetic Acid↗

Acute and chronic stress effects on open field activity in the rat: implications for a model of depression.

The initial activity of a rat placed in novel surroundings (i.e., open field activity) has been taken as an indicator of its emotional state. We have investigated the effects of immediately antecedent stress upon open field activity in comparison with basal (i.e., unstressed) activity, and additionally, the effects of a history of chronic stress upon the above behavioral patterns. Acute exposure to a non-traumatic, non-debilitating stress (noise and light) consistently increased activity in comparison with basal activity. A history of chronic stress on the other hand reduced basal activity from control levels, and eliminated the activation response to acute stress. This lack of acute activation may bear some resemblance to depression on several grounds. Behaviorally it represents a "refractory loss of interest." Also, chronically stressed rats showed endocrine changes similar to those seen in human depressives. Finally, antidepressant treatment with the monoamine oxidase inhibitor pargyline restored the ability of chronically stressed rats to respond actively to stress.

Acute Disease↗

Amphetamine and tranylcypromine in an animal model of depression: pharmacological specificity of the reversal effect.

Amphetamine and tranylcypromine are structurally related chemical isomers with pharmacologically distinctive activity profiles. Since they are equimolar and structurally similar they may be used to assess the pharmacologically distinctive activity profiles. Since they are equimolar and structurally similar they may be used to assess the pharmacological specificity of a proposed animal model of depression. Adult male Sprague-Dawley rats were exposed to a chronic stress regimen or remained undisturbed. They were then acutely stressed with white noise. The monoamine oxidase inhibitor tranylcypromine was effective in restoring otherwise reduced stress elicited open field activity in chronically stressed rats. Amphetamine did not resemble tranylcypromine or other antidepressants, and produced a variety of effects at least some of which indicated a potential increase rather than reduction in depression consequent to chronic administration.

Amphetamine↗

Changes in rat hypothalamic and brain stem catecholamine concentrations following acute administration of phenylethanolamine-N-methyltransferase inhibitors.

The effect of acute phenylethanolamine-N-methyltransferase (PNMT) inhibition on rat brain catecholamine concentrations was studied. All PNMT inhibitors tested were effective in depleting hypothalamic and brain stem epinephrine. Norepinephrine concentrations were unaffected; however, dopamine levels were increased in all areas studied. While several possible explanations are offered for this phenomenon, the mechanism is not yet understood.

Animals↗

Tail pinch facilitation of self-stimulation in the rat--dependence upon dopamine and independence of opiates.

We have previously demonstrated that adult male Sprague-Dawley rats which are chronically maintained upon a schedule of intracranial reward (ICS) show elevated rates of response after a mild tail pinch. Both dopamine and opiates have been implicated in the mediation of other stress induced behavioral alterations, and may therefore also possibly be involved in the ICS effect. The present report replicated the initial finding of tail pinch induced facilitation of ICS, and further demonstrated that while opiate blockade failed to affect the ICS response dopaminergic blockage in fact inhibited it. These findings suggest neuropharmacological specificity for stress related behavioral change, and further implicate dopamine in stress responses.

Animals↗

Stress, behavioral arousal, and open field activity--a reexamination of emotionality in the rat.

The effects of stress upon emotionality, and of emotionality upon the open field activity of rats have now been studied for over four decades. Controversy remains however regarding the degree to which stress alters behavior, and the direction of that change. One reason for this is the absence of an adequate behavioral definition of stress. The present series of experiments demonstrates a standard relatively nontraumatic stress induction procedure which may be used in conjunction with open field testing. Pre-exposure to moderately intense light and white noise facilitated open field activity as measured by initial activity, lowered defecation scores, and supplementary measures (rearing, grooming, center field penetration). Further parametric, psychoendocrine, and pharmacological studies characterized the nature of the facilitation, its time course, and its modification by other manipulations. Our results suggest the initial behavioral response to stress in an open field is activation. Previous studies may have differed in their results relating stress and behavior because of subtle procedural distinctions, some of which may be identified using the present technique.

Adrenal Glands↗

Stress induced grooming in the rat--an endorphin mediated syndrome.

Exposure of adult male Sprague--Dawley rats to a non-traumatic noise-light stress procedure subsequently increased grooming behavior in a novel environment. The grooming syndrome was marginally facilitated by adrenalectomy and by hypophysectomy. Opiate blockade by naltrexone returned grooming to basal levels. This suggests that stress induced grooming is not dependent upon pituitary-adrenal integrity for its expression, although it may be modulated by the latter. On the other hand this form of grooming may depend upon an endogenous opiate system.

Adrenalectomy↗

Immunohistochemical localization of dynorphin (1-8) in hypothalamic magnocellular neurons: evidence for absence of proenkephalin.

Dynorphin(1-8) immunoreactivity was visualized by immunohistofluorescence in hypothalamic magnocellular neurons of the rat. No immunoreactive met-enkephalin-Arg6-Gly7-Leu8, a fragment of the adrenal medulla pro-enkephalin molecule, was detected in magnocellular neurons. However, a strong met-enkephalin-Arg6-Gly7-Leu8-like immunostaining was seen in other regions of the brain. These results suggest that in magnocellular neurons dynorphin(1-8) exists independently from pro-enkephalin and therefore the magnocellular neurons represent a third opioid peptide neuronal system in brain. These observations, however, do not rule out a coexistence of proenkephalin and dynorphin-related peptides in other regions of the brain.

Animals↗