PubMed Health⌕ Search

Biomedical subjects

Neil E Rowland

Publications and source records attributed to Neil E Rowland.

At least 19 recordsLinked to original sources
PubMed2006

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice.

Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination. The neuropathogenesis of the disease has not been completely elucidated, however, oxidative stress is considered to be a key feature of the disease process. Hyperphenylalanemia also adversely affects monoaminergic metabolism in the brain. For this reason we chose to evaluate the nigrostriatum of Pah(enu2) mice, to determine if alterations of monoamine metabolism resulted in morphologic nigrostriatal pathology. Furthermore, we believe that recent developments in adeno-associated virus (AAV)-based vectors have greatly increased the potential for long-term gene therapy and may be a viable alternative to dietary treatment for this metabolic disorder. In this study we identified neurodegenerative changes with regenerative responses in the nigrostriatum of Pah(enu2) mice that are consistent with oxidative injury and occurred as early as 4 weeks of age. These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to Pah(enu2) mice and corresponded to rapid reduction of serum Phe levels.

Amino Acid Oxidoreductases↗
PubMed2006

Effects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats.

Previous studies have indicated that apelin, a novel peptide suggested to have some actions related to angiotensin peptides, has either a dipsogenic or an antidipsogenic effect and either increases or decreases blood pressure. The present study attempts to provide replication or understanding of these disparate effects. Neither central (lateral or third cerebral ventricle) nor peripheral (intravenous) administration of apelin induced water intake in sated rats, nor did it decrease water intake in deprived rats. It also had no effect on sodium appetite. Peripherally injected apelin had a hypotensive action in anesthetized rats, but had no consistent effect in awake, unrestrained rats. We conclude that apelin does not have reliable or robust effects on fluid intake or blood pressure in Sprague-Dawley rats under normal conditions, but discuss the possibility for a role of apelin in fluid homeostasis in selected physiological states.

Animals↗
PubMed2006

Characteristics of salt appetite in chronically sodium-depleted rats using a progressive ratio schedule of procurement.

Satiation of sodium appetite of rats was studied using a protocol of sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. In the first experiment in which NaCl was freely available from a drinking spout, rats consumed substantially more hypertonic NaCl than their estimated physiological deficit. In the second and third experiments, a simulated foraging cost was imposed on obtaining NaCl. In these experiments, rats were required to perform a progressive ratio lever press task to procure aliquots of hypertonic NaCl, and under these conditions they showed a break point or satiation for NaCl when they had consumed an amount close to their estimated deficit. In the fourth experiment, we found that the chronic diuretic regimen produced hypovolemia along with large increases in plasma aldosterone concentration and renin activity, and that all of these parameters were reversed toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Examination of natriuresis revealed that excessive intake of NaCl had no lasting benefit in this protocol: NaCl consumed in excess of need on 1 day was completely lost at the subsequent diuretic treatment. In the final two experiments, we showed that oral preloads of NaCl had no significant effect on progressive ratio procurement of NaCl, but that oral preloads reduced subsequent oral drinking. The data are discussed in terms of definitions of satiation of appetite in regard to the tightly regulated domain of body fluid homeostasis, and by extension, their relevance to systems such as energy homeostasis where set points appear to be less tightly regulated.

Aldosterone↗
PubMed2005

Sodium preference and appetite in rats in an operant protocol.

An operant task that may simulate natural foraging was used to study in Sprague-Dawley rats the need-free choice between water and various concentrations of NaCl solution, and the induction of sodium appetite during chronic deoxycorticosterone acetate (DOCA) treatment. The task imposed a fixed ratio foraging or procurement cost for access to each fluid. The relative preference for NaCl over water when both had the same procurement cost was similar to the preference/aversion function that has been reported for this strain of rat under free drinking conditions. As the procurement cost increased, the number of bouts taken per day of both water and NaCl decreased and the mean bout size increased. Administration of DOCA produced an increase in NaCl intake under all conditions, and this appetite was manifest as discrete episodes whose frequency and size were inversely related. Natural observations of sodium appetite in mammals, such as excursions to, often remote, mineral deposits, imply an episodic organization of this behavior. This report is the first laboratory simulation of environmental factors that affect the episodic or temporal organization of sodium appetite.

Animals↗
PubMed2005

Accurate caloric compensation in rats for electively consumed ethanol-beer or ethanol-polycose mixtures.

High elective intake of ethanol was achieved in rats by presenting ethanol in palatable vehicles. We simultaneously measured intake of food (chow) to assess the accuracy of caloric compensation for the energy in the alcoholic commodity. In the first study, we used beer; nonalcoholic beer was consumed in large amounts, and when 5% or 10% ethanol was added, intake amounted to approximately 10% of daily calories. In the second study, Polycose in either solution or a gel matrix was used as the palatable vehicle for ethanol. The intake of ethanol was even higher than in the beer study, particularly in the gel preparation. In all cases, both male and female rats showed accurate caloric compensation by a reduction in chow intake. In a final study, we showed that restricted time access to the Polycose-alcohol gel produced high elective intakes and substantial blood alcohol levels. Over 24 h, caloric compensation was again accurate. Thus, unlike some reports in humans, rats seem able to compensate accurately for alcohol calories and in particular when, as with most alcohol consumption by humans, these are presented in palatable vehicles.

Animals↗
PubMed2005

Effect of two types of environmental enrichment for singly housed mice on food intake and weight gain.

For animals that cannot be housed socially for scientific reasons, such as rodents on food intake-energy expenditure studies, the provision of environmental enrichment may alleviate stress. However, the influence of environmental enrichment on food intake and energy expenditure is unresolved. The authors tested the effects of two environmental enrichment options on food intake and weight gain in singly housed mice. Their results may be helpful in developing rodent enrichment programs.

Analysis of Variance↗
PubMed2004

Role of angiotensin in body fluid homeostasis of mice: effect of losartan on water and NaCl intakes.

It is known that mice injected peripherally with ANG II do not show a drinking response but that cFos immunoreactivity (ir) is induced in brain regions similar to those in rats. We now show in Crl:CD1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SFO). Injection of ANG II into the lateral cerebral ventricle produced a robust water intake in mice and induced Fos-ir in SFO, as well as in median preoptic (MnPO) and paraventricular (PVN) nuclei. Peripheral injection of losartan blocked this drinking response and prevented the induction of Fos-ir in each of these brain regions. Hypovolemia produced by polyethylene glycol (PEG) produced a robust water intake but no evidence of sodium appetite, and it induced Fos-ir in SFO, MnPO, and PVN. Peripheral injection of losartan did not affect this drinking response. Fos-ir induced by PEG in SFO and MnPO was reduced by treatment with losartan, while that induced in the PVN was further increased by losartan. Sodium depletion with furosemide and low-sodium diet produced a strong sodium appetite and induced Fos-ir in SFO and MnPO. Treatment with losartan completely blocked the sodium appetite, as well as the induction of Fos-ir in these brain regions. These data indicate that endogenous production of ANG II and action at forebrain receptors is critically involved in depletion-related sodium appetite in mice. The absence of an effect of losartan on PEG-induced drinking suggests the critical involvement of other factor(s) such as arterial or venous baroreceptor input, and we discuss how this factor could also explain why peripheral ANG II is not dipsogenic in mice.

Angiotensin II↗
PubMed2004

Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine.

Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala. This attenuation is similar to that described previously in rats. Because loss of efficacy of these agents could be related to loss of 5-HT transporter (5-HTT) sites, their presumptive primary mode of action, in the final study we determined the effect of various, low-dose regimens of D-F and D-NF on 5-HT uptake in frontal cortex of mice and rats. We show in mice that D-F causes a greater loss of 5-HT uptake than D-NF, and that at the lowest dose regimen used uptake was unaffected in rats but was reduced in mice. The data are discussed in terms of the species difference in behavioral tolerance and differences in neurochemical profile of D-F and D-NF.

Animals↗
PubMed2004

Sodium deficiency and salt appetite in ICR: CD1 mice.

Using an outbred strain of mouse, we examined several characteristics of sodium appetite induced by depletion. We found that an appetite for 0.15 M NaCl solution was stimulated 24 h after injection of furosemide and access to a low-sodium diet, but not by low-sodium diet alone. When the duration of exposure to low-sodium diet was increased from 1 to 7 days, there was no additional effect on either the appetite or the blood plasma changes including elevated hematocrit ratio, protein and aldosterone concentrations, and plasma renin activity (PRA). Mice also showed an appetite for hypertonic (0.5 M) NaCl in solutions or in a gel matrix; the intakes of these two were comparable but the gel measurement was gravimetric so maybe more accurate. In the same study, we showed that single injections of either 10 or 40 mg/kg furosemide followed by a 24-h low-sodium diet produced similar appetites, but that 2.5 mg/kg had a submaximal effect. Lastly, we further validated the use of the gel matrix by showing in chronically depleted mice that intake was inversely related to NaCl concentration in the range 0.5-1.5 M, and that appetite was selective for sodium but not the anion with which it was paired.

Analysis of Variance↗
PubMed2004

The vagus nerve and thirst.

This paper reviews the experiments, which demonstrate conclusively the involvement of the abdominal vagus nerve in normal expression of most aspects of thirst in rats, by Gerard P. Smith and his colleagues published between 1975 and 1984. The nature of that vagal contribution differs with the type of primary thirst signal. Thus, there is no clear or unitary answer concerning whether the contribution of the vagus nerve is purely sensory, or some general tonic action within the central nervous system. Subsequent studies using cFos mapping of intracellular dehydration in conjunction with vagotomy and/or hepatic manipulations are also reviewed and further illustrate the involvement of abdominal information, both in the initiation as well as the termination of drinking. Many of the questions that were raised by Smith during these pioneering studies remain unaddressed and unanswered.

Angiotensins↗
PubMed2003

LiCl-induced flavor avoidance compared between rats and mice using a nondeprivation protocol.

The present studies examine some parameters involved in flavor avoidance learning, using LiCl to induce malaise, in a novel nondeprivation protocol that allows direct comparison between rats and mice. The procedure involves daily presentation of a gelatin dessert that contains carbohydrate (Polycose) and a distinctive food flavor. Regular chow is additionally available at all times. Both rats and mice showed robust intakes of these gels with little change of gram intake as concentration of Polycose was varied in the range 2-30%; at the highest concentration, the caloric yield was approximately 7% of normal daily intake in both species. Rats that were injected on three occasions with LiCl (0.75 meq/kg) 1 h after consumption of a flavored gel formed a complete and sustained conditioned flavor avoidance (CFA). In a two-flavor discrimination protocol, in which a second flavor was followed by injections of saline, rats showed complete avoidance of the LiCl-paired flavor and partial avoidance of the saline-paired flavor. Mice injected on three occasions with LiCl (6 meq/kg) 1 h after intake of a flavored gel formed a partial CFA; a more complete CFA was formed when there was no delay between removal of the flavor and the injection. Using this no-delay protocol, mice, like rats, showed avoidance of a saline-paired flavor in a two-flavor discrimination protocol, and the CFA was strong when the dose of LiCl was reduced to that used in rats (0.75 meq/kg). In comparable protocols, mice thus are able to form complete CFAs using low doses of LiCl that are comparable to CFAs observed in rats, but the interval between flavor and sickness over which associative learning can occur may be shorter in mice.

Animals↗
PubMed2003

Brain muscarinic receptor subtypes mediating water intake and Fos following cerebroventricular administration of bethanecol in rats.

RATIONALE: The brain regions and receptor subtypes involved in water intake following central cholinergic stimulation have been incompletely characterized. OBJECTIVES: To examine whether drinking and brain Fos-immunoreactivity (ir) induced in rats by central administration of bethanecol is reversed by either the preferential M1 antagonist pirenzepine, the M3 antagonist 4-DAMP, or their combination. METHODS: Male Sprague-Dawley rats were surgically implanted with cerebroventricular cannulae. The muscarinic agonist, bethanecol was used as the dipsogenic agent. Either nonselective (atropine) or selective muscarinic receptor antagonists were injected together with bethanecol to determine blockade of drinking. In parallel studies, Fos-ir was assessed in discrete brain regions. RESULTS: Bethanecol-induced drinking was completely blocked by atropine or by a combination of pirenzepine and 4-DAMP; these latter antagonists alone produced sub-total inhibition of drinking. In contrast, water intake induced by angiotensin II was unaffected by combination of pirenzepine and 4-DAMP. Fos-ir was induced by bethanecol in many brain regions previously implicated in body fluid regulation, including subfornical organ and the magnocellular supraoptic and paraventricular hypothalamic nuclei. Induced Fos-ir was substantially but not completely prevented by co-injection of either pirenzepine or 4-DAMP, but their combination did not seem markedly more effective than either alone. CONCLUSIONS: Drinking induced by brain muscarinic receptor stimulation seems to proceed by a combination of M1 and M3 receptor subtypes. Drinking induced by angiotensin II occurs independently of this mechanism. Fos-ir induced in fluid-related brain regions by bethanecol either uses additional receptor type(s) or is less easily blocked than drinking behavior.

Animals↗
PubMed2003

Role of angiotensin in body fluid homeostasis of mice: fluid intake, plasma hormones, and brain Fos.

CD1 mice injected peripherally with either ANG I or ANG II failed to drink substantial amounts of water or NaCl, yet showed strong Fos immunoreactivity (ir) in subfornical organ (SFO). Mice injected with furosemide showed modest stimulation of NaCl intake either 3 or 24 h later, were hypovolemic, and showed elevated plasma renin activity (PRA). The pattern of Fos-ir in the brain after furosemide was similar to that seen after peripheral injection of ANG II. Mice became hypovolemic after subcutaneous injection of polyethylene glycol (PEG), showed large increases in PRA, aldosterone, and water intake, but did not show sodium appetite. PEG-treated mice had strong activation of SFO as well as other brain regions previously shown to be related to ANG-associated drinking in rats. ANG II appears to have a modified role in the behavioral response to fluid loss in mice compared with rats.

Aldosterone↗
PubMed2003

Effect of repeated administration of dexfenfluramine on feeding and brain Fos in mice.

The present study examines whether repeated administration of dexfenfluramine (DFEN) to mice is associated with progressive attenuation of its anorectic action and induction of Fos-immunoreactivity (Fos-ir) in some brain regions, both known effects in rats. ICR:Cd-1 mice were adapted to receiving for 30 min daily a sweetened milk gelatin dessert in addition to ad libitum access to chow. Mice were then injected with either DFEN (5-10 mg/kg) or saline vehicle every other day. These doses of DFEN acutely suppressed intake by approximately 50% and this action was sustained for at least eight injections. The anorectic effect of DFEN was no different between drug-naïve and DFEN-pretreated mice under conditions that produce complete tolerance in rats. In addition, unlike in rats, the acute anorectic effect of m-chlorophenylpiperazine (mCPP) was unaffected by prior DFEN treatment. Mice were perfused after the intake test on the final experimental day and their brain processed for Fos-ir. DFEN induced Fos-ir in brain regions analogous to those reported in rats and, also, as in rats, DFEN pretreatments reduced substantially the Fos-ir induced by acute DFEN in regions including central nucleus of amygdala, bed nucleus of stria terminalis, and the paraventricular hypothalamus (magno- and parvocellular divisions; PVN). Thus, while DFEN pretreatments reduce the effects of DFEN in many brain regions in both rats and mice, mice are unlike rats insofar as there is no tolerance to the anorectic action, at least in the nondeprivation protocol used here.

Animals↗
PubMed2003

Meal patterns of lean and leptin-deficient obese mice in a simulated foraging environment.

C57BL/6J lean and obese (lep -/-) mice were studied in a closed economy operant protocol that simulates foraging. A predetermined number of presses on a procurement lever (PFR) activated a consumatory lever on which presses would produce 20-mg food pellets. Mice could eat as much as they wished but, once no responding occurred for an elapsed 10-min period, the consumatory lever was inactivated and the procurement or foraging cycle began again. Under these conditions, as has been shown for rats and other species, mice initiated relatively discrete meals (about nine per day) at the lowest PFR, and the number of meals initiated per day decreased with increasing PFR. Meal size increased reciprocally, so that total intake was conserved across the range of PFR examined. Obese mice ate larger meals than lean mice at low PFR, and showed further increases but only at the highest PFRs. The small and inconsistent literature on meal patterns in mice is reviewed, and we discuss the utility of the present protocol to study the interactions between genetic and environmental economic factors, and their implications for the etiology of human obesity.

Animals↗
PubMed2003

Sodium appetite induced in rats by chronic administration of a thiazide diuretic.

Characteristics of hydrochlorothiazide (HCZ)-induced sodium appetite were examined in rats fed with low sodium diet to which HCZ was added. Compared with controls, HCZ induced a robust appetite for 0.1 and 0.3 M NaHCO3. The intake of 0.3 M NaCl was only about one half that of NaHCO3, but was still greatly above control. In both cases, the intake of the sodium solution exceeded that of water, so the rats were taking a hypertonic mixture. The appetite was evident in both Sprague-Dawley and Long-Evans rats, but appeared to be more stable in the latter strain over at least 1 month. The diuretic and natriuretic effect of HCZ was sustained over this period. Plasma renin activity was elevated substantially in HCZ-treated rats, but aldosterone concentration was decreased. Administration of HCZ in food is a simple and reliable method for inducing a sustained, substantial, and need-based salt appetite in rats.

Animals↗