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R McCarty

Publications and source records attributed to R McCarty.

At least 19 recordsLinked to original sources
PubMed1999

Attenuation of morphine-induced behavioral changes in rodents by D- and L-glucose.

Administration of d-glucose enhances learning and memory in several tasks and also attenuates memory impairments and other behavioral effects of several drugs, including morphine. The present experiment compared the effects of peripherally administered d-glucose with those of l-glucose, a stereoisomer of d-glucose that is not metabolized and does not readily cross the blood-brain barrier. Like d-glucose, though at somewhat different doses, peripherally administered l-glucose attenuated morphine-induced deficits in spontaneous alternation performance in rats and mice and attenuated morphine-induced hyperactivity in mice. l-Glucose did not raise circulating levels of plasma d-glucose, suggesting that the effects of l-glucose are not secondary to increased availability of d-glucose. Using direct injections of d- and l-glucose and morphine into the medial septum of rats, the findings indicate that d-glucose but not l-glucose attenuated morphine-induced deficits in spontaneous alternation performance; indeed, intraseptal injections of l-glucose alone impaired spontaneous alternation performance. These findings suggest that peripheral l-glucose antagonizes morphine-induced behavioral effects by a peripheral signaling mechanism, one distinct from the mechanisms that mediate at least some of the effects of d-glucose on brain function.

Animals↗
PubMed1999

Enhanced release of norepinephrine in rat hippocampus during spontaneous alternation tests.

Recent evidence suggests that release of acetylcholine (ACh) in the hippocampus is associated with performance on a spontaneous alternation task and with enhancement of that performance by systemic and central injections of glucose. The present study extended these findings by examining norepinephrine (NE) release in the hippocampus using in vivo microdialysis while rats were tested for spontaneous alternation performance with and without prior injections (ip) of glucose. Microdialysis samples were collected every 12 min and assayed for NE content by HPLC-ECD. Like ACh, NE release in hippocampus increased during spontaneous alternation testing. As in past experiments, administration of glucose (250 mg/kg) significantly enhanced alternation scores. However, glucose did not influence NE release either during behavioral testing or at rest. These findings contrast with prior evidence showing that glucose augments testing-related increases in ACh release. The findings suggest that norepinephrine is released within the hippocampus while rats are engaged in alternation performance. However, increased release of norepinephrine apparently does not contribute to the enhancement of alternation scores produced by glucose.

Animals↗
PubMed1999

Altered NGF regulation may link a genetic predisposition for hypertension with hyperactive voiding.

PURPOSE: Hyperactive voiding and elevated smooth muscle NGF output are traits of the spontaneously hypertensive rat (SHR). Elevated target-derived NGF is associated with hypertension and hyperactive voiding in SHRs. In the present study, we tested for possible genetic links between hypertension, hyperactive voiding and augmented bladder smooth muscle cell (BSMC) NGF secretion. MATERIALS AND METHODS: We crossed SHRs with WKYs to produce a gene segregating F2 population. We measured F2 mean arterial blood pressure (BP) and six-hour voiding frequency. BSMCs were cultured from 'Low BP F2s' (95+/-2) and 'High BP F2s' (141+/-3 mm. Hg) and conditioned medium tested for NGF with a two-site ELISA. The NGF regulators isoproterenol, platelet-derived growth factor (PDGF) and phorbol-12-myristate-13-acetate were tested in F2 BSMC cultures. RESULTS: A positive correlation (r = 0.75) between blood pressure and voiding frequency existed in this F2 population. As BP rose voiding frequency increased and volume per void decreased such that there were no significant changes in total urine voided (Low BP F2s: 1.0+/-0.5; High BP F2s: 6.2+/-0.5 voids/6 hours). Low BP F2s (2.0+/-0.2) secreted NGF at a higher basal rate than High BP F2s (0.7+/-0.1 fg NGF/hr/100 cells). However, High BP F2s (1,620 and 3,850) were oversensitive to isoproterenol and PDGF-induced increases in NGF output, compared with Low BP F2s (219 and 1,282% control, respectively). CONCLUSIONS: Elevated tissue NGF due to a hypersensitivity to NGF regulating stimuli, rather than alterations in basal NGF, may genetically link hypertension and hyperactive voiding.

Animals↗
PubMed1998

Arterial nerve growth factor (NGF) mRNA, protein, and vascular smooth muscle cell NGF secretion in hypertensive and hyperactive rats.

Elevated levels of nerve growth factor (NGF) protein and NGF mRNA have been reported in the vessels of spontaneously hypertensive rats (SHR: hypertensive, hyperactive) compared to Wistar-Kyoto (WKY) rats. Elevated NGF may be involved in the development of hypertension in SHRs. We examined vascular NGF mRNA and protein content and the regulation of NGF secretion by vascular smooth muscle cells (VSMCs) from two inbred strains (WKHT: hypertensive; WKHA: hyperactive) derived from SHRs and WKYs. Our goal was to determine if receptor-mediated defects in NGF regulation play a role in increased secretion of VSMC NGF from hypertensive animals. Tissue NGF mRNA content was determined by competitive, quantitative RT-PCR. Tissue NGF and NGF content in cultured VSMC-conditioned medium was quantified using a two-site ELISA. Tail artery NGF mRNA was elevated in WKHTs compared to WKHAs. Tissue NGF protein was elevated in WKHT aorta, mesenteric, and tail artery compared to WKHAs. Pharmacologically induced increases in NGF output were blocked with inhibition of transcription or protein synthesis. Basal NGF secretion by WKHT VSMCs was significantly higher than WKHAs. The observed increases in VSMC NGF output in SHRs over WKYs in response to beta-adrenergic agents are not preserved in the WKHT:WKHA comparison. Protein kinase C-dependent increases in SHR VSMC NGF appear in both WKHTs and WKHAs. In contrast, elevated NGF levels due to disturbances in alpha-adrenergic, peptidergic, and purinergic control of NGF output are features common to both genetic models of hypertension (SHR and WKHT). These results suggest that the defect in smooth muscle NGF metabolism observed in SHRs cosegregates with a hypertensive rather than a hyperactive phenotype. Moreover, altered receptor-mediated regulation (alpha-adrenergic, peptidergic, and purinergic) of VSMC NGF production may contribute to elevated vascular tissue NGF, suggesting a mechanism leading to the high levels of NGF associated with hypertension in SHRs and WKHTs.

Adenosine Triphosphate↗
PubMed1998

Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats.

The effect of prenatal stress was investigated on the sympathoadrenal response to novelty and footshock by measuring the time course of the changes in circulating corticosterone (COR) catecholamines and their metabolites. Pregnant rats were subjected to noise and light stress, three times weekly on an unpredictable basis throughout gestation. When the male offspring of stressed rats (PS) and those of unstressed mothers (C) were 4.5-5 months of age, they were prepared with indwelling catheters in the tail artery 24 h before the experiment. Resting levels of plasma COR, noradrenaline (NA), adrenaline (AD), dihydroxyphenylglycol (DHPG), dihydroxyphenylacetic acid (DOPAC), and dihydroxyphenylalanine (DOPA) were measured. Further blood samples were taken within 3 min of their transfer to the shock box, 1-2, 5, 15, and 45 min after footshock. Plasma COR was significantly higher in PS than in C rats at rest, but those of adrenaline, NA, and their metabolites did not differ in the two groups. Transfer of the rats to the shock box increased plasma COR, NA, adrenaline, and dihydroxyphenylglycol in both groups, and dihydroxyphenylalanine and dihydroxyphenylacetic acid only in PS rats. All the catechols increased further 2-3 min after footshock, except dihydroxyphenylalanine in PS rats. Plasma NA and dihydroxyphenylglycol levels were significantly higher in PS than in C rats immediately after footshock, indicating a greater activation of the sympathetic nervous system in PS rats. The findings demonstrate for the first time that prenatal stress can induce long term changes in the sensitivity of the sympathoadrenal system to stress.

Animals↗
PubMed1998

Neurally mediated hyperactive voiding in spontaneously hypertensive rats.

The development of hypertension in spontaneously hypertensive rats (SHR) and hyperactive voiding in rats with urethral obstruction are characterized by abnormal smooth muscle growth, increased tissue levels of nerve growth factor (NGF) and altered patterns of innervation. The present study was undertaken to determine if bladder smooth muscle from SHRs contains and secretes elevated levels of NGF, and if so, whether the augmented NGF contributes to changes in bladder innervation and function without tissue hypertrophy. Voiding behavior was monitored using specially designed metabolic cages. NGF levels in tissue homogenates and conditioned cell culture media were measured by ELISA. NGF mRNA in cultured bladder smooth muscle cells (BSMCs) was quantified using reverse transcriptase PCR. Noradrenergic innervation was assessed by staining with glyoxylic acid and assaying norepinephrine (NE) content in bladders with high performance liquid chromatography. SHRs voided more frequently than WKY rats. NGF content was higher in bladders from adult SHRs when compared to Wistar-Kyoto normotensive rats (WKYs). No significant difference in NGF mRNA content was observed between SHR and WKY BSMCs. However, SHR BSMCs secreted NGF at a higher rate and amount per unit mRNA than did WKY BSMCs. SHR bladders contained more NE and were more densely stained for catecholaminergic fibers than bladders from WKY rats. The results support the hypothesis that elevated NGF secretion by bladder smooth muscle is associated with hyperinnervation of bladder and hyperactive voiding in SHRs. Thus, the SHR strain may represent a genetic model to study changes in bladder function resulting from altered patterns of innervation.

Adrenergic Fibers↗
PubMed1998

Activity-dependent regulation of dopamine content in the olfactory bulbs of naris-occluded rats.

Several lines of evidence strongly suggest that reduced olfactory nerve activity results in decreased bulb dopamine content. In the present study, high performance liquid chromatography with electrochemical detection was used to assess catecholamine levels in bulbs from postnatal day 60 rats that had undergone either unilateral naris cautery or a sham surgery on day 30. Thirty days of odor deprivation dramatically reduced dopamine and dihydroxyphenylacetic acid levels in functionally-deprived bulbs (ipsilateral to occluded nares) as compared to contralateral controls, while norepinephrine and dihydroxyphenylglycol levels were unchanged. The loss of dopamine was more severe in medial as compared to lateral aspects of experimental bulbs, while the loss of dihydroxyphenylacetic acid was similar on the two sides. To test directly the hypothesis that afferent activity regulates dopamine and dihydroxyphenylacetic acid content, 1 h of high frequency tetanic nerve stimulation was provided to the rostral-medial olfactory nerve layer in deprived olfactory bulbs, and catecholamine levels were assessed from 6 to 192 h later. Partial and temporary recovery of dopamine was observed in medial aspects of the bulb when rats were examined 96 h later, while consistent recovery of dihydroxyphenylacetic acid content was not apparent. These data corroborate evidence that olfactory nerve activity is a potent regulator of bulb dopamine and indicate that continued afferent input is necessary to maintain dopamine levels.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding.

Elevated bladder smooth muscle cell (BSMC) nerve growth factor (NGF) secretion and related neuroplasticity are associated with hyperactive voiding in spontaneously hypertensive rats (SHRs: hypertensive, behaviorally hyperactive), compared with control Wistar-Kyotos (WKYs). We used two inbred strains (WKHT: hypertensive; WKHA: hyperactive) to further investigate this phenomenon. WKHA BSMCs secreted higher basal levels of NGF than WKHT BSMCs. Antagonists did inhibit NGF output in WKHA but not WKHT cultures. Thus augmented basal secretion of NGF cosegregates with a hyperactive phenotype, whereas a lack of regulatory inhibition of NGF output cosegregates with a hypertensive phenotype. Bladder norepinephrine content paralleled NGF content, with WKHTs > SHRs > WKHAs > WKYs, providing evidence that a lack of inhibition is the greatest contributor to elevated bladder NGF and noradrenergic innervation. Protein kinase C (PKC) agonists affected NGF production differentially depending on strain, suggesting that altered PKC signaling may contribute to strain differences in NGF secretion. Finally, 6-h voiding frequency differed between the strains, with SHRs > WKHTs = WKHAs > WKYs. Thus aspects of both the hypertensive and hyperactive phenotypes may be associated with elevated SHR bladder NGF and hyperactive voiding.

Animals↗
PubMed1997

Efferent and afferent neuronal hypertrophy associated with micturition pathways in spontaneously hypertensive rats.

Elevated nerve growth factor secreted by bladder smooth muscle may be associated with noradrenergic hyperinnervation of the bladder and hyperactive voiding in spontaneously hypertensive rats (SHR) and rats with bladder outlet obstruction. The present study was undertaken to determine if changes occur in efferent and afferent pathways supplying the SHR bladder similar to those in rats with bladder outlet obstruction. Fluoro-Gold (FG) retrograde tracing studies were conducted to examine the postganglionic efferent limb (major pelvic ganglion; MPG) and sensory afferent limb (L1, L2, L6, and S1 dorsal root ganglion; DRG) of the micturition reflex pathway of the SHR and Wistar-Kyoto (WKY) normotensive rat. A significant increase in cross sectional area profiles for labeled neurons in the MPG was observed in SHRs (830.5 +/- 9.0 microns2) as compared to WKYs (736.3 +/- 16.6 microns2). Neuronal cell areas in L2 (1,010.9 +/- 18.6 microns2) and S1 (1,024.6 +/- 28.3 microns2) of SHRs were significantly larger than those of WKYs (L2, 865.3 +/- 12.6 microns2, S1, 778.3 +/- 11.2 microns2). There was an increase in number of labeled cells in L6 within SHRs over WKYs. These results provide evidence that both efferent and afferent changes in neuronal innervation of the bladder occur in SHRs. The SHR strain may represent a genetic model to study changes in micturition reflex pathways that result from alterations in neuronal morphology such as those that occur with urethral outlet obstruction.

Animals↗
PubMed1997

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats.

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.

Journal Article↗
PubMed1996

Age and stress history effects on spatial performance in a swim task in Fischer-344 rats.

This study determined whether prior habituation to water immersion would ameliorate age-related deficits in learning and memory in a swim task. Aged (22 months) and young adult (3 months) rats were immersed in water (30 degrees C) for 15 min on each of 28 consecutive days before training in the swim task. Additional groups of age-matched animals served as handled controls. Training on a spatial discrimination version of the water task was conducted over 5 days with two trials per day (1-h intertrial interval). A probe trial was substituted for the last trial on the fifth day to assess the rats' use of spatial information. Three days later, rats received cue discrimination training to find a visible platform. In the spatial task, prior habituation to water immersion ameliorated deficits in acquisition within each day (i.e., at a 1-h intertrial interval) but not across days (at 24 h). The results obtained with the 24-h interval confirm the rapid forgetting characteristic of aged rats in many tasks. The stress-habituation procedures reduced age-related deficits seen on the probe trial and on cue discrimination training. These findings indicate that several aspects of age-related impairments in the swim task, often attributed to primary age-related deficits in learning and memory processes per se, may instead be secondary to age-related differences in stress responses to water immersion.

Aging↗
PubMed1996

Maternal influences on adult blood pressure of SHRs: a single pup cross-fostering study.

To examine the effects of the preweanling maternal environment on the development of adult blood pressure, individual spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive pups were reciprocally cross-fostered between mothers of the same or opposite strain. With this design, each SHR and WKY foster mother reared 7 of her own pups and 1 SHR or WKY foster pup. All litters were weaned at 21 days of age and body weights were obtained. At 110 days of age, SHR and WKY males were weighed and surgically prepared with chronic tail artery catheters. One day later, basal measures of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats per min) were obtained while animals were resting and undisturbed in their home cages. Our findings indicate that adult SHRs reared by WKY foster dams displayed significant reductions in MAP compared to SHRs that were reared by their natural mothers or by SHR foster mothers. In contrast, MAPs of WKYs did not differ across rearing conditions. Weanling body weights of cross-fostered SHRs were significantly greater than control-reared SHRs while weanling body weights of cross-fostered WKYs were significantly lower than control-reared WKYs. However, by 110 days of age, there were no treatment-related effects on body weights of males of either strain. These findings underscore the importance of genotype x maternal environment interactions during the preweanling period for the development of cardiovascular phenotype in SHRs.

Animals↗
PubMed1996

Preweanling administration of terazosin decreases blood pressure of hypertensive rats in adulthood.

To examine the contribution of the sympathetic nervous system to the development of hypertension, we injected spontaneously hypertensive rat (SHR) pups and normotensive Wistar-Kyoto rat (WKY) pups twice daily with saline (1.0 mL/kg SC) or terazosin (0.5 mg/kg SC), an alpha 1-adrenoceptor antagonist, from postnatal day 1 through 21. We determined the effectiveness and duration of action of this terazosin dose in pilot studies with adult SHR and WKY. Body weights of WKY pups were greater than body weights of SHR pups from postnatal day 1 through 21. In addition, body weights of terazosin-treated pups of both strains were comparable to body weights of saline-injected littermate controls. Indirectly measured systolic pressures of terazosin-treated SHR were reduced significantly at 60 and 90 days of age but not at 30 days of age compared with saline-injected littermate controls. Terazosin did not affect systolic pressures of WKY, measured at 30, 60, and 90 days of age. At 100 days of age, in chronically catheterized rats, mean arterial pressures of terazosin-treated SHR were reduced significantly compared with those of saline-injected littermate controls. In contrast, terazosin did not affect mean arterial pressures of WKY at 100 days of age. Finally, preweanling treatment with terazosin did not alter patterns of open field behavior of adult SHR or WKY. SHR were significantly more active and reared more frequently compared with WKY. These findings indicate that the time between birth and weaning at 21 days of age is critical for the full expression of the hypertensive phenotype in SHR. Chronic blockage of alpha 1-adrenoceptors during the preweanling period in SHR may reduce vascular hypertrophy, leading to long-term reductions in arterial pressure.

Adrenergic alpha-Antagonists↗
PubMed1995

Effects of immobilization on in vivo release of norepinephrine in the bed nucleus of the stria terminalis in conscious rats.

Release of norepinepriine (NE) and its metabolites in the bed nucleus of the stria terminalis (BNST) was examined using in vivo microdialysis in conscious rats before, during and after 2 h of immobilization. Microdialysate levels of NE and of dihydroxyphenylglycol (DHPG) increased by 170-290% above basal levels during the 1st h of immobilization and decreased gradually thereafter. In contrast, levels of dihydroxyphenylacetic acid (DOPAC) increased gradually over the entire period of immobilization, peaking at 110% above baseline levels. These findings indicate that in rats a single immobilization is attended by increased synthesis, release and reuptake of NE within the BNST. The results are consistent with previous findings relating to stress-induced release of NE in the hypothalamic paraventricular nucleus, central nucleus of the amygdala and cerebral cortex and suggest concurrent noradrenergic activation in several brains centers during acute stress.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Age-related changes in plasma catecholamine responses to acute swim stress.

Young adult (3 months) and aged (22 months) Fischer 344 male rats were prepared with chronic tail artery catheters. Three days after surgery, rats were exposed acutely to swim stress at 20, 25, 30, or 35 degrees C for 15 min. Blood samples were obtained from each rat under basal conditions, at the end of the swim stress episode, and 15, 30, and 45 min after swim stress. Basal plasma levels of norepinephrine and epinephrine (EPI) were similar for 3- and 22-month-old rats. In contrast, plasma catecholamine responses of aged rats were significantly greater than those of young adult rats following swim stress at 20 and 25 degrees C. Plasma catecholamine responses were similar for rats of the two ages following swim stress at 30 or 35 degrees C. These findings indicate that aged rats have exaggerated sympathetic-adrenal medullary responses to acute swim stress at the lower water temperatures. Given the modulatory effects of plasma EPI on memory, these age-related alterations in plasma catecholamine responses to acute swim stress may influence spatial memory performance of rats in the Morris water maze.

Aging↗