Biomedical subjects

C Prasad

Publications and source records attributed to C Prasad.

At least 73 records · Page 4Linked to original sources

PubMed1994

Differential modulation of dopaminergic systems in the rat brain by dietary protein.

Rats that consume a diet 50% rich in protein exhibit hyperactivity and hyperresponsiveness to nociceptive stimuli, in which facilitation of dopaminergic activity has been implicated. We studied the regional changes in the concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brains of rats that were maintained on high-protein (HP, 50% casein), normal-protein (NP, 20% casein), and low-protein (LP, 8% casein) diets for 36 weeks. Brain nuclei that represented different DAergic systems were punch-dissected and analyzed using HPLC. In the substantia nigra, the striatum, and the dentate gyrus, DA concentrations decreased and increased, respectively, with a decrease and increase in dietary protein (p < 0.05 compared to the NP diet). Similar trends in the effect of the HP diet were observed in the ventral tegmental area, amygdala, frontal cortex, subiculum, centromedial nucleus (CM) of the thalamus, and inferior colliculi (IC), although the differences in DA concentrations were not statistically significant. These brain areas also showed a pattern of decreased DA concentration in association with the LP diet, and the differences were statistically significant (p < 0.05) in the CM and IC. DA concentrations in most regions of the midbrain and brainstem were not different between the diet groups, nor were consistent trends observed in those regions. Also, there were no consistent relationships between DOPAC/DA and HVA/DA ratios and dietary protein level. These data suggest that only discrete dopaminergic neuronal circuits in the rat forebrain were sensitive to changes in dietary protein level.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Chronic nicotine reverses age-associated increases in tail-flick latency and anxiety in rats.

The chronic consumption of low doses of nicotine in drinking water for two years consistently increased the sensitivity of rats to a nociceptive thermal stimulus (tail-flick test), but reduced aversiveness in the elevated plus-maze test, relative to the responses of age-matched controls in these tests. The responses of aged nicotine-consuming rats were indistinguishable from those of young adult rats that did not receive nicotine. To determine whether these effects were due to a nicotine-induced retardation of age-related changes, young adult rats were similarly treated with nicotine for three months and similar changes in the tail-flick latency and performance in the plus-maze test were observed during nicotine consumption. These changes were reversed following withdrawal from nicotine. It is concluded that the maintenance of circulating low levels of nicotine (and/or its metabolites) increased the nociceptive sensitivity of the rats and reduced their aversions in the plus-maze test regardless of their age.

Aging↗

PubMed1994

Individual differences in the macronutrient preference profile of outbred rats: implications for nutritional, metabolic, and pharmacologic studies.

While screening outbred male Holtzman Sprague-Dawley rats for their macronutrient (protein, carbohydrate, and fat) preferences, we noticed substantial group-to-group variation in the preference profile. This led us to analyze preference data on two hundred and seventy rats collected over a three-year period to determine whether preferences could be predicted. The results led us to conclude that observed variations in macronutrient preference profiles may be secondary to genetic heterogeneity in the outbred population. We have also shown that the outcome of the pharmacologic effects of two agents (insulin and enterostatin) on appetitive behavior will vary from animal to animal within a single group. Accordingly, researchers must be aware that the breeding history of the laboratory animal is a major factor in the outcome of the experiment and interpretation of the findings.

Animal Nutritional Physiological Phenomena↗

PubMed1994

Chronic nicotine intake decelerates aging of nigrostriatal dopaminergic neurons.

We have evaluated the effect of chronic nicotine intake on the age-associated loss of nigrostriatal dopaminergic neurons. The striatal density of dopamine (D1 and D2) receptors and DA-uptake sites decreased with age. Concomitant with these changes was a pronounced loss of many behavioral functions associated, at least in part, with dopaminergic neurotransmission. Chronic oral intake of nicotine resulted in partial restoration of the loss of receptors as well as behavioral performances. The results suggest that low doses of nicotine could have beneficial effects during aging.

Aging↗

PubMed1994

Does cyclo(His-Pro) act like amphetamine?

In many pharmacologic tests, cyclo(His-Pro) (CHP) appears to act like a dopaminergic agonist and augments the actions of amphetamine (AMP). Therefore, to determine whether CHP is an AMP-like peptide, a comparison between CHP and AMP was made using four separate tests known to be AMP-responsive. These include, food intake, locomotor activity, dopamine uptake and modulation of binding sites for amphetamine and mazindol. A decrease in food intake and increase in spontaneous locomotor activity and stereotypy was observed after peripheral administration of amphetamine but not CHP. Chronic CHP administration resulted into a decrease in striatal amphetamine - and increase in mazindol-binding sites; in contrast, chronic amphetamine decreased both amphetamine - and mazindol-binding sites. These results show a clear dissociation between CHP and AMP suggesting that CHP is not an amphetamine-like peptide.

Animals↗

PubMed1994

Stress-related behavior and central norepinephrine concentrations in the REM sleep-deprived rat.

Rapid eye movement sleep deprivation (REMd) is a potent stressor in the rat. Behavioral abnormalities are among the earliest overt symptoms of REMd, the mechanisms for which remain largely unknown. The phenomena of hyperphagia and weight loss that are associated with REMd may contribute to its later morbidity; however, little is known about the onset of these phenomena or the neurotransmitter mechanisms that are involved. The aim of this study was to determine whether the earliest effects of REMd on consumatory behavior in the rat and its performance in the swimming cylinder of Porsolt are related to changes in norepinephrine (NE) concentrations in the cerebral cortex and selected areas of the hypothalamus. Sprague-Dawley rats were divided into three groups (n = 6): the REMd group resided in a water tank on 6.5-cm diameter pedestals for 96 h; the tank control (TC) group resided in the water tank on 15-cm pedestals for 96 h; the cage controls (CC) remained in their home cages for the duration of the study. In the first series of experiments, body weights and caloric intake were recorded daily, along with the performance of all animals in the swimming cylinder of Porsolt. In the second series of experiments, body weights and caloric intake were recorded, but the Porsolt test was not employed and the brains were dissected after 96 h for NE analysis by HPLC. It was observed that the REMd group had lower immobility times (p < 0.05) in the Porsolt test after only 24 h, compared to groups TC and CC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult↗

PubMed1994

Role of endogenous cyclo(His-Pro) in cold-induced hypothermia in the desert rat (Mastomys natalensis).

Central administration of exogenous cyclo(His-Pro) (CHP) is known to produce hypothermia in rodents. In the present study, we examined the role of endogenous CHP in cold-induced hypothermia in the desert rat, Mastomys natalensis. The results of these studies show that a rise in hypothalamic CHP content accompanied a decrease in rectal temperature during cold exposure. Immunoneutralization of endogenous CHP resulted in a significant decline in cold-induced hypothermia. In addition, central administration of cyclo(Ala-Gly), a structural analogue of CHP, also led to a decrease in cold-induced hypothermia. The results of these studies show that changes in endogenous CHP levels may affect body temperature regulation.

Analysis of Variance↗

PubMed1994

Corticosterone facilitation of inhibition of fat intake by enterostatin (Val-Pro-Asp-Pro-Arg).

Enterostatin or Val-Pro-Asp-Pro-Arg (VPDPR) is the amino-terminal pentapeptide of procolipase; VPDPR is generated during tryptic activation of procolipase to lipase. In rodents, exogenous VPDPR has been shown to cause a selective decrement in fat appetite. To understand the mechanism(s) underlying the action of this peptide, we have studied the effects of corticosterone, an adrenal hormone known to modulate caloric intake, on VPDPR-mediated inhibition of appetite. The results of this study show a significant increase in the inhibition of total caloric intake by 250 micrograms/kg VPDPR following corticosterone treatment (control, 2.3%; corticosterone treated, 22.7%). Furthermore, the decrement in the caloric intake in corticosterone-treated rats was exclusively due to the loss of fat intake.

Amino Acid Sequence↗

PubMed1993

Bidirectional changes in striatal D1-dopamine receptor density during chronic ethanol intake.

Results of previous studies on the effects of ethanol consumption on the properties of D1 dopamine receptors appear contradictory and inconclusive. In this study we have examined the time course of the effects of dietary ethanol on the properties of striatal D1 dopamine receptors. Chronic ethanol intake led to bidirectional changes in the maximum number (Bmax) of [3H]SCH-23390 binding to striatal D1 dopamine receptors measured 10 hrs after termination of the ethanol intake. A significant decrease (80% of control), increase (159% of control), increase (122% of control), and decrease (85% of control) after 1, 2, 3, and 4 weeks of ethanol intake respectively was observed. The bidirectional changes disappeared after 6 and 10 weeks of continued ethanol intake and the Bmax returned back to the control level. The receptor affinity (Kd), however, remained unaltered in all cases. These data suggest that the duration of ethanol exposure may be an important determinant in regulating D1 dopamine receptor density.

Animals↗

PubMed1993

Regulation of dietary fat preference: establishing a reproducible profile of dietary fat preference in rats.

The mechanism(s) underlying preference for individual macronutrients (particularly fat) in diet are poorly understood. The greatest obstacle in designing experiments to define neurochemical determinants of fat preference lies in our ability to clearly identify animals' macronutrient preference (MP) profile. To this end, we have defined the role of several variables and suggested ways to design better studies to examine the mechanism of macronutrient preference. The results of these studies show that the paradigm used for MP analysis, genetics and age of the animal could clearly affect the MP profile.

Aging↗

PubMed1993

Effects of rapid eye movement sleep deprivation on the properties of striatal dopaminergic system.

Using the water tank procedure, we have examined the effects of rapid eye movement (REM) sleep deprivation and associated stress on the properties of striatal dopaminergic system. While stress decreased the number of D1 and D2 dopamine receptors, a combination of REM sleep deprivation attenuated the decrease. The ratio of D1 to D2 densities, however, increased on both the stress and REM sleep deprivation groups. In contrast, the number of dopamine uptake sites remained unchanged. The enhanced behavioral responses to dopaminergic stimulants after REM sleep deprivation are discussed.

Animals↗

PubMed1992

Decreased striatal D2 dopamine receptors in obese Zucker rats: changes during aging.

The specific binding of [3H]YM-09151-2 was used to investigate the possible differences in age-associated changes in striatal D2 dopamine (DA) receptor properties in genetically obese (fa/fa) Zucker rats and their lean (Fa/?) littermates. The maximal binding sites (Bmax) of D2 DA receptors was found to decline with age in both obese and lean rats; the rate of decline in receptor Bmax was slightly higher in lean than obese rats. However, the Bmax of D2 DA receptor in 6-, 12- and 18-month-old obese rats was significantly lower compared to the age-matched lean rats. These data indicate that obesity decreases the number of striatal D2 DA receptors without affecting the rate at which receptor number decreases with age.

Aging↗

PubMed1992

Production and characterization of a monoclonal antibody to dopamine D2 receptor: comparison with a polyclonal antibody to a different epitope.

A monoclonal antibody (Mab) that recognizes the rat dopamine D2 receptor (DAR) has been generated using DAR specific peptide. The Mab, IgM isotype recognizes five proteins (Mr 220, 145, 95, 66 and 47 kDa) in striatal membrane on Western blot. Preincubation of Mab with free peptide blocked the labeling of all five bands. A polyclonal antibody against peptide from a different region of the DAR, reacted with three out of five proteins (220, 66, and 47 kDa) in these membranes. The DAR antagonist NAPS-biotinyl binds to a 220 kDa protein in striatal membrane on ligand blotts; the labeling can be blocked by the addition of 2 microM sulpride. The 220 kDa Mab reactive protein was less in cerebellum and was absent in the liver. Neither the Mab nor polyclonal antibody inhibited binding of a DAR antagonist, [3H]YM09151-2, to the striatal membranes. These antibodies will enable us to study the structure/function and regulation of the synthesis of DAR protein.

Amino Acid Sequence↗

PubMed1992

Localization of dopamine D2 receptor protein in rat brain using polyclonal antibody.

The precise distribution of the dopamine type D2 receptor has been mapped for the first time in rat brain using an antibody to D2 receptor protein. Polyclonal antisera were collected from rabbits inoculated with an undecapeptide identical to residues 24-34 of the D2 protein sequence. Rat brain slices, 40 microns in thickness, were incubated with either primary antiserum, the antiserum plus free peptide antigen, or pre-immune serum. Antibody binding was visualized by peroxidase-antiperoxidase (PAP) reaction followed by light microscopy. PAP complex bound moderately-to-densely throughout the medial forebrain bundle, and was seen in more discrete regions in the midbrain, consistent with the binding of D2 radioligands. There were some unexpected results, namely in the cerebral cortex and nucleus accumbens, there were unexpectedly steep gradients in binding density, decreasing caudally; no binding was detected in the hippocampus or the substantia nigra pars reticulata. In all positive-staining regions examined, the antibody was highly localized to neuronal cell bodies, except in the frontal cortex where antibody was also evident on basilar dendrites. These data confirm that the polyclonal antibody recognized dopamine D2 receptor protein throughout the rat brain, and suggest that the D2 receptor is distributed more abundantly on somata than on cellular processes.

Animals↗

PubMed1992

Alterations in dendritic spine density in the rat brain associated with protein malnutrition.

Rats that consume a high-protein diet are hyperactive, hyperresponsive to noxious stimuli, and demonstrate elevated basal arousal levels. Although the mechanism involved in dietary protein-induced changes in behavior is unclear, it may involve many changes including abnormal dendrite morphology in the brain. Three groups of rats were pair-fed with isocaloric diets containing 8%, 20% and 50% casein for 4 weeks. Their brains were processed for examination of dendritic spine densities in the frontal, parietal, and entorhinal cortices, the striatum, and the septum. Animals on the 50% casein diet showed increased spine densities in all areas investigated (P less than 0.05), compared to the animals on normal (20%) casein. In contrast, animals maintained on the 8% casein diet showed increased spine densities (P less than 0.05) only in the striatum and entorhinal cortex, and exhibited normal densities in the frontal and parietal cortices, and the medial septum.

Animals↗

PubMed1992

Post-transcriptional regulation of loss of rat striatal D2 dopamine receptor during aging.

The mechanism(s) underlying age-associated diminutions in the rat striatal D2 dopamine receptor (D2-receptor) number was investigated. The levels of D2-receptor mRNA in 4-, 12- and 18-month-old rat striata were found not to change. In contrast, the levels of 110 kDa protein, labeled with a D2-receptor specific antibody, decreased in parallel with [3H]YM-09151-2 binding to striatal membranes. These data suggest a role for post-transcriptional mechanism(s) in age-associated decrease in D2-receptor.

Actins↗

PubMed1992

A low protein-high carbohydrate diet decreases D2 dopamine receptor density in rat brain.

The property of D2 dopamine receptors in the rat brain was evaluated after long-term dietary manipulation. Groups of rats were pair-fed with equicaloric diet containing low protein (8%)-high carbohydrate, high protein (52%)-low carbohydrate and normal protein (20%) for 36 weeks. The low protein-high carbohydrate fed rats exhibited a significant decrease in the density (Bmax) of D2 dopamine receptor in the striatum (28%) and the mesolimbic regions (36%) with no apparent change in the receptor affinity (Kd). These findings suggest that long-term consumption of a low protein-high carbohydrate diet, by decreasing D2 dopamine receptor density, may be an important determinant of central dopaminergic function.

Animals↗