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Biomedical subjects

C M Kuhn

Publications and source records attributed to C M Kuhn.

At least 91 records · Page 5Linked to original sources
PubMed1985

Effect of chronic methadone administration on neuroendocrine function in young adult rats.

This study reports the endocrine effects of chronic methadone (METH) administration. Two treatment regimens were tested: a constant (5 mg/kg/day, CD) or increasing dose (5 mg/kg twice daily, increasing 1 mg/kg/day, ID). Basal hormone levels and endocrine responses to opiate challenge were determined on days 5, 10 and 20 and after withdrawal. METH effects on hormone secretion varied with treatment duration, dose and hormone. Tolerance to METH effects on corticosterone (CS), prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH) and luteinizing hormone (LH) developed during the ID regimen and basal CS, TSH and LH levels were altered. In addition, serum testosterone, T3 and T4 decreased significantly during this regimen. In contrast, only CS secretion was affected markedly by the CD regimen. Resting levels were elevated by day 5 and the CS response to acute METH challenge was reversed. Tolerance also developed to METH-induced TSH suppression, but only with longer treatment. Similarly, basal TSH and LH levels were affected only with longer treatment. Basal PRL, GH and LH levels and LH, PRL and GH responses to acute METH challenge were not affected by the CD regimen. Changes in basal CS and TSH levels observed in these studies probably reflect abstinence, as even more pronounced changes occurred after naloxone-precipitated abstinence and suppressed rather than reversed responses were observed if animals were withdrawn for 36 hr before testing. Tolerance in some endocrine systems appears to be quite long-lasting, as CS, TSH and PRL responses to METH challenge were still decreased 3 weeks after withdrawal from the ID regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1984

Effect of chronic methadone administration on neuroendocrine function in developing rats.

This paper reports the effects of chronic postnatal methadone administration on basal hormone levels and on the endocrine response to methadone. Chronic postnatal methadone administration delayed normal developmental increases in serum T4 (decrease on day 5), corticosterone (CS) (days 15 and 20) and growth hormone (GH) (day 25). In addition, marked tolerance to methadone effects on GH, CS, thyroid-stimulating hormone (TSH) and prolactin (PRL) secretion developed during chronic postnatal administration, and effects on PRL and TSH secretion persisted after drug withdrawal.

Age Factors↗
PubMed1984

Behavioral manipulation of the diabetic phenotype in ob/ob mice.

The genetically obese mouse (C57BL/6J ob/ob) is a commonly used model of non-insulin-dependent diabetes mellitus. However, our studies demonstrate that, while the animal is significantly hyperinsulinemic, it in fact does not show consistent hyperglycemia in the resting state. During stress, both obese animals and their lean littermates become hyperglycemic, but the magnitude of the hyperglycemia is exaggerated in the obese mice. Obese animals also show an exaggerated plasma glucose increase in response to epinephrine injection. This increase in plasma glucose is accompanied by a decrease in plasma insulin in response to both stress and epinephrine. Our findings suggest that environmental stimuli influence the expression of diabetes in the C57BL/6J obese mouse and therefore must be considered in studies of this animal model of diabetes.

Animals↗
PubMed1983

Endocrine effects of methadone in rats; acute effects in adults.

The effects of methadone (METH) on serum levels of prolactin (PRL), growth hormone (GH), corticosterone (CS), TSH and T4 were determined in male and female rats. METH initially (15-45 min after injection) decreased TSH and increased PRL, GH and CS in both male and female rats. These changes were followed by a rebound decrease in CS and increase in TSH 4 h after METH administration. METH decreased GH at 0.1 mg/kg, but increased secretion with doses of 0.5 mg/kg and higher. Changes in PRL, CS and TSH were only seen with 1 mg/kg and higher. Naloxone blocked increases in serum GH, PRL and CS and the decrease in TSH caused by METH. Serum PRL increased significantly more in females than in males, although other endocrine actions of METH were the same in males and females. Pretreatment of animals with METH 4 h before a second challenge dose did not affect TSH, PRL or GH responses to METH. However, peak CS levels were lower in pretreated animals than in controls. These findings demonstrate that METH elicits a complex profile of endocrine response which probably reflects actions at multiple receptor and/or anatomical sites, and suggest that reported sex differences in METH metabolism are not limiting in determining the hormonal response to this drug. These results also suggest that single-dose tolerance develops to the effects of METH on CS but not on other endocrine parameters.

Aging↗
PubMed1983

Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats.

Chronic continuous infusion of norepinephrine (NE) or epinephrine (Epi) subcutaneously in rats resulted in rapid elevation of systolic blood pressure (SBP) by 40 mm Hg. Pressure remained high for the duration of the infusion but rapidly returned to control levels after its termination. Pronounced hypertrophy of the thoracic aorta, abdominal aorta and heart was evident within 2 days of the initiation of NE infusion and a plateau was attained by 5 days of infusion. The activity of tissue ornithine decarboxylase (ODC), the rate limiting enzyme in polyamine biosynthesis, was elevated preceeding the onset of tissue hypertrophy, and returned to control levels coincidentally with the cessation of accelerated tissue growth. It is concluded that high blood pressure in this animal model of hypertension is dependent upon the continued presence of exogenous catecholamine, and that pronounced cardiovascular hypertrophy per se is not sufficient to maintain the hypertension. The elevation and decline of vascular ODC activity is consistent with reports that in other tissues an elevation of ODC activity is an obligatory early event in hypertrophy.

Animals↗
PubMed1983

Ontogeny of endocrine responses to methadone in rats.

The effects of methadone (METH) on serum levels of prolactin (PRL), growth hormone (GH), corticosterone (CS) and TSH were determined in developing rats. METH increased PRL, GH and CS and decreased TSH at all ages tested, but the time course and magnitude of these effects changed during ontogeny. METH effects on day 10 were lower in magnitude than those observed in adults. In 20 day old pups, METH effects on GH and CS were comparable to those of adults, but TSH effects were still blunted. METH effects on hormone secretion in both 10 and 20 day old pups lasted longer than those observed in adults. Naloxone blocked all hormonal responses in adults, but did not completely block METH effects on CS secretion in 10 day old pups.

Aging↗
PubMed1983

Ontogeny of stress effects on ornithine decarboxylase activity in rats.

This study demonstrates that "stress" elicits a specific pattern of organ response in developing rats that is determined by the particular "stress" and by the age of the animal. Maternal deprivation (MD) of preweanling rat pups decreases ornithine decarboxylase (ODC) activity in many tissues, as reported previously, while immobilization (IMM) and cold stress increase ODC activity in liver and heart of neonatal rat. Serum GH is decreased by MD and by IMM, but is not affected by cold stress. Stress-induced ODC elevation increases with age, while MD effects disappear at weaning. IMM and cold increase ODC activity in kidney, liver and heart of adult rats. These effects of IMM are blocked by the ganglionic antagonist chlorisondamine in adult but not in neonatal rats. The results of this study suggest that MD and the "classical" stress paradigms IMM and cold evoke different patterns of organ ODC response in neonatal rats. Furthermore, these findings suggest that the mechanism by which immobilization increases ODC activity changes from a hormonal to a neural mechanism during ontogeny.

Animals↗
PubMed1983

Lack of potency of metoclopramide's metabolites in various dopaminergic models.

The dopaminergic properties of metoclopramide and four of its metabolites were determined in a series of in vivo and in vitro tests. In vivo measures included changes in dopamine turnover, serum prolactin levels and antagonism of apomorphine-induced stereotyped behavior. In each of these tests the four metabolites were either completely inactive or significantly less potent than the parent compound. The potency of metoclopramide and its metabolites in in vitro dopamine/neuroleptic receptor models was compared to the potency of standard reference compounds. In vitro results indicate that none of the four metabolites tested had antagonist activity in any of the receptor models in which they were evaluated. These findings will be discussed in light of the current understanding of receptor models as they relate to antipsychotic efficacy.

Animals↗
PubMed1983

Selective loss of ornithine decarboxylase response to adrenergic agonists and glucagon during food deprivation of neonatal rats.

We have previously reported that maternal deprivation of rat pups causes a decrease in tissue responsiveness to growth hormone that is mediated by the loss of maternal tactile stimulation. We now report that liver responses to alpha and beta adrenergic agonists as well as glucagon and vasopressin decrease during maternal deprivation. However, the decreased responsiveness to these agents is mediated by short-term food deprivation (FD) rather than loss of maternal tactile stimulation. When 8-day-old rat pups were separated from the mother or placed with a nipple-ligated mother for 2 hr and then injected with phenylephrine, isoproterenol or glucagon, liver ornithine decarboxylase (ODC) activity did not increase, although ODC activity increased markedly in control pups after administration of these agents. This loss of responsiveness appears to be both tissue- and drug-specific, as liver ODC responses to dexamethasone, dibutyryl cyclic AMP and prostaglandin E-1 and heart ODC responses to phenylephrine were not affected. FD had only a slight effect on glycogen phosphorylase activation by phenylephrine and had no effect on phenylephrine-induced glycogen depletion. Finally, FD did not affect the number of alpha-1 or beta receptors in liver of rat pups. These findings suggest that short-term FD selectively decreases liver ODC responses to certain agonists including alpha and beta adrenergic agonists by postreceptor mechanisms.

Adrenergic alpha-Agonists↗
PubMed1983

Ontogeny of rat hepatic adrenoceptors.

Hepatic alpha-1, alpha-2 and beta-2 adrenoceptors were characterized during development of the rat through Scatchard analysis of [3H]prazosin, [3H]rauwolscine and [125I]pindolol binding to liver membrane preparations. Major changes in adrenoceptor numbers occur shortly before birth at weaning. The fetal rat liver is characterized by a large number of alpha-2 adrenoceptors, which falls 10-fold by birth. The number of hepatic beta-2 adrenoceptors decreases gradually during development, and is lower at all times than the number of alpha-1 and alpha-2 adrenoceptors. The developmental profile of the hepatic alpha-1 adrenoceptor is biphasic: there is a 2 to 3-fold fall in alpha-1 adrenoceptor number at birth and a 3- to 5-fold rise at weaning. While absolute numbers of alpha-1 and beta-2 adrenoceptors do not correlate precisely with reported actions of epinephrine and norepinephrine on hepatic metabolism during ontogeny, the increasing ratio of alpha-1/beta-2 hepatic adrenoceptors may contribute to the conversion from predominantly beta effects of catecholamines reported in fetal and suckling rat liver to the predominantly alpha-1 effects that are well documented in the adult male rat.

Animals↗
PubMed1983

Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain.

Tetrabenazine (TBZ) is used in the treatment of hyperkinetic movement disorders. Its effect is thought to be mediated by depletion of dopamine (DA) stores. We studied other possible mechanisms of action of this drug. TBZ decreased DA concentration in rat striatum and nucleus accumbens in a dose-dependent manner with an IC50 of approximately 1.2 mg.kg-1. Maximal depletion was obtained within 30 min with only partial recovery at 8 hr. TBZ induced (at 40 mg . kg-1) 5- to 8-fold increases in 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations in both brain regions. Unlike reserpine, TBZ completely abolished the apomorphine-induced inhibition of DA synthesis under conditions in which this effect is mediated by presynaptic DA receptors. Both TBZ (5 mg . kg-1) and reserpine (5 mg . kg-1) depleted, at 1 hr, striatal DA content by approximately 90%. However, TBZ, but not reserpine, significantly stimulated in vivo tyrosine hydroxylase activity. TBZ also inhibited [3H]spiperone binding in the striatum with Ki = 2.1 X 10(-6) M. In rats, with unilateral destruction of the nigrostriatal pathway with 6-hydroxydopamine, pretreatment with TBZ significantly reduced the number of rotations induced by apomorphine. Finally, in rats treated with either TBZ (5 mg . kg-1) or reserpine (5 mg . kg-1), prolactin levels significantly increased as compared to control values. TBZ, but not reserpine, blocked apomorphine inhibition of prolactin secretion. We conclude that, in addition to depleting monoamines, TBZ also blocks both presynaptic and postsynaptic DA receptors in rat brain.

Animals↗
PubMed1982

Norepinephrine content of the rat kidney during development: alterations induced by perinatal methadone.

The concentration and the total content of norepinephrine (NE) in the kidney were measured in Sprague-Dawley rats from 3 to 120 days after birth. Renal NE concentration was relatively low until the end of the second week, when it rose abruptly to adult levels; total NE content per kidney increased steadily throughout development. The effects of perinatal methadone treatment on renal NE development were examined by administering the drug either directly to the pups from 1 to 19 days after birth, or to the mother from 10 days of gestation to 20 days after birth. Both treatments resulted in significant deficits of body weight and kidney weight. Maternal methadone caused a significant deficit in renal NE which was most pronounced at two weeks of postnatal age; direct methadone had less effect on renal NE. These results suggest that renal sympathetic neurotransmission may become mature two weeks after birth and indicate further that maternal methadone interferes with this maturation.

Animals↗
PubMed1982

Type A behavior and elevated physiological and neuroendocrine responses to cognitive tasks.

Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.

Behavior↗
PubMed1982

Maturation of growth hormone stimulation of kidney ornithine decarboxylase in the rat.

The effect of ovine growth hormone (GH) on kidney ornithine decarboxylase (ODC) was studied in newborn, preweanling and young adult rats. Basal kidney ODC activity was very low from 4 to 22 days after birth but rose 20-fold by day 25; it remained elevated through day 45. GH failed to stimulate ODC in the first two weeks after birth. GH did however stimulate ODC markedly from 20 through 45 days. Kidney ODC was stimulated in the neonate by vasopressin and by isoproterenol, but not by angiotensin II. Liver ODC remained relatively low and stable during development, and was responsive to GH at all ages studied. We conclude that a) the pattern of development of basal kidney ODC appears to be unique to this tissue and may be related to the postnatal maturation of renal morphology and/or function, b) neonatal kidney ODC is unresponsive to certain hormones but is not completely refractory to stimulation. These findings may have implications for the role of hormones in the maturation of the kidney and in the regulation of early renal function.

Age Factors↗
PubMed1981

Effect of 5,7-dihydroxytryptamine on serotonergic control of prolactin secretion and behavior in rats.

The intracisternal administration of 5,7-dihydroxytryptamine (5,7-DHT) to rats resulted in a potentiated response to 5-hydroxytryptophan (5-HTP) when the animals were tested 30 days later. The 5-HTP-induced changes include elevation of serum prolactin, decrease in operant responding, and the magnitude of the "serotonin behavioral syndrome" observed after 5-HTP administration. The serotonin concentration in brains of 5,7-DHT-treated animals reached maximum earlier and remained elevated longer than that of controls following administration of 5-HTP. Brain norepinephrine and dopamine concentration were not affected by 5-HTP in either group of animals. The increase in serum prolactin concentration elicited by administration of the serotonergic agonists quipazine or 5-methoxy-N,N-dimethyltryptamine and by the serotonin uptake inhibitor fenfluramine also was potentiated by pretreating rats with 5,7-DHT. These data suggest that both serotonergic receptor supersensitivity and the absence of presynaptic uptake sites contribute to the enhanced responses to 5-HTP occurring in rats previously treated with 5,7-DHT. The findings further demonstrate that both behavioral and hormonal measures can be used to assess the sensitivity of serotonergic receptors and indicate that 5,7-DHT may be useful in evaluating the role of serotonergic neurons in neuroendocrine function.

5,7-Dihydroxytryptamine↗
PubMed1981

Maturation of central nervous system control of growth hormone secretion in rats.

The concentration of growth hormone (GH) in serum of neonatal rats was determined by radioimmunoassay after administration of various drugs that after serum GH in adult rats. Administration of the serotonin precursor 5-hydroxytryptophan or morphine increased serum GH in pups of all ages. The 5-hydroxytryptophan-induced rise was prevented by the serotonergic antagonist cyproheptadine but not by the dopaminergic antagonist haloperidol. Pentobarbital decreased serum GH in 5-day-old pups but increased GH in 15-, 20- and 35-day-old pups. Clonidine decreased serum GH in 5- and 10-day-old pups and did not increase serum GH until pups were 35 days old. Finally, significant ultradian surges of GH secretion were observed in 35-day-old animals but only slight secretory episodes occurred in 24-day-old pups. These results suggest that the serotonergic and endogenous opiate systems involved in regulation of GH secretion in rats are functional within the first postnatal week. In contrast, the extrahypothalamic mechanisms through which pentobarbital acts do not mature until 2 to 3 weeks after birth. Finally, the inability of clonidine to stimulate GH secretion and the absence of significant ultradian surges before day 35 suggest that the noradrenergic mechanism and possibly other neural systems which trigger the surges of GH secretion observed in adult rats do not mature until after puberty.

5-Hydroxytryptophan↗