Level of satiety: GABA and pentose shunt activities in three brain sites associated with feeding

1985 ◽  
Vol 248 (4) ◽  
pp. R453-R458 ◽  
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin

The hypothesis addressed was that metabolic activity within specific brain areas may be altered to depict peripheral metabolic status. Sixty-three female Sprague-Dawley rats (225 g) received 150, 100, or 50% of normal intake by gastric intubation for 7 days. The incentive for spontaneous feeding would be inhibited in 150% fed rats (anoretic), stimulated in 50% fed rats (hungry), and maintained in 100% fed rats (control). Glucose flux through the gamma-aminobutyric acid shunt of the ventrolateral hypothalamus was 32% lower in hungry rats and 35% higher in anoretic rats relative to control values. Glucose flux through the pentose shunt of the ventromedial hypothalamus was 111% lower in hungry rats and 152% higher in anoretic rats relative to control values. Pentose shunt activity in the area postrema nucleus of the solitary tract (AP NTS) was 116% lower in hungry rats and 60% higher in anoretic rats relative to control values; however, hungry and anoretic rats had AP NTS pentose shunt activities that were not different from control values but were different from each other. The data demonstrate that within selective brain sites, specific pathways for glucose oxidation are affected by energy intake and may be used by the rat to assess and respond to changes in peripheral energy status.


2002 ◽  
Vol 30 (04) ◽  
pp. 507-519
Author(s):  
Sue Yu ◽  
Yee-Yung Ng ◽  
Zhi-Hong Jian ◽  
Chien-Chih Chen ◽  
Mei-Shiun Lu ◽  
...  

Levels of monoamines and metabolites, excitatory amino acids, and γ-aminobutyric acid (GABA) were investigated in discrete brain areas of chronic Jiawey Siwu (JS)-treated rats. Male Sprague-Dawley rats were dosed orally for 3 months with normal saline or JS at 0.21, 1.05 or 4.2 g/kg/day. Body weights of these four groups were similar over 3 months. Most effects of JS revealed a dose dependency with levels of neurotransmitters. Levels of norepinephrine (NE) and epinephrine (EPI) in cerebral cortex; EPI, vanillylmandelic acid (VMA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in medulla oblongata; DA in midbrain; NE and 5-HT in amygdala; and 5-HT in hypothalamus had decreased in JS-treated rats. 3-Methoxytyramine (3-MT) in cerebral cortex; 5-hydroxyindole-3-acetic acid (5-HIAA) in medulla oblongata; NE, 3-MT and homovanillic acid (HVA) in pons; EPI and 3-MT in midbrain; 3-MT and HVA in amygdala; 3-MT, 3,4-dihydroxyphenylacetic acid (DOPAC), HVA and 5-HIAA in cerebellum; HVA in hypothalamus; and DOPAC and HVA in hippocampus had all increased in JS-treated rats. In pons, 5-HT increased with low and decreased with high JS doses. Ratios of DA/3-MT in pons and midbrain; DA/HVA in pons and cerebellum; and 5-HT/5-HIAA in medulla oblongata, cerebellum and hypothalamus had decreased. Furthermore, aspartate (ASP) and glutamate (GLU) levels had decreased in cerebral cortex, midbrain, hypothalamus and hippocampus or amygdala, and increased in pons. GABA levels were reduced in cerebral cortex, and higher in medulla oblongata, pons, amygdala, cerebellum, hippocampus and striatum of JS-treated rats. These results indicate that the synthesis and (or) metabolism of NE, DA, EPI and 5-HT, and the levels of ASP, GLU and GABA in rat brains were differentially regionally altered by JS, which may contribute to the central manifestations of JS treatment.



Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4375
Author(s):  
Hyesook Lee ◽  
Hyun Hwangbo ◽  
Seon Yeong Ji ◽  
Min Yeong Kim ◽  
So Young Kim ◽  
...  

Bone growth during childhood and puberty determines an adult’s final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 μg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.



Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 131-138 ◽  
Author(s):  
Betilay Topkara ◽  
Hasan R. Yananli ◽  
Eren Sakallı ◽  
Mahluga Jafarova Demirkapu

Aims: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. Methods: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day. Results: Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups. Conclusion: These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.



Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.



1990 ◽  
Vol 68 (9) ◽  
pp. 1194-1199 ◽  
Author(s):  
U. Ebert ◽  
K. Krnjević

A new potent, blood–brain barrier permeable γ-aminobutyric acid (GABA) uptake blocker, 1-[2-[bis[4-(trifluoromethyl)-phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-966) was administered systemically by i.p. injection (5 mg/kg) in Sprague–Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there was a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region. Like the effect of nipecotic acid (applied locally by iontophoresis), the potentiation by CI-966 was clearest when GABA was applied in or near the stratum pyramidale where its action normally is weakest and shows the most pronounced fading. This change in GABA potency is most simply explained by a reduction in GABA uptake.Key words: GABA, muscimol, nipecotic acid, GABA-uptake blocker, epilepsy.



2013 ◽  
Vol 304 (11) ◽  
pp. H1538-H1546 ◽  
Author(s):  
Brittany S. Luckett ◽  
Jennifer L. Frielle ◽  
Lawrence Wolfgang ◽  
Sean D. Stocker

Accumulating evidence suggests that insulin acts within the hypothalamus to alter sympathetic nerve activity (SNA) and baroreflex function. Although insulin receptors are widely expressed across the hypothalamus, recent evidence suggests that neurons of the arcuate nucleus (ARC) play an important role in the sympathoexcitatory response to insulin. The purpose of the present study was to determine whether circulating insulin acts directly in the ARC to elevate SNA. In anesthetized male Sprague-Dawley rats (275–425 g), the action of insulin was neutralized by microinjection of an anti-insulin affibody (1 ng/40 nl). To verify the efficacy of the affibody, ARC pretreatment with injection of the anti-insulin affibody completely prevented the increase in lumbar SNA produced by ARC injection of insulin. Next, ARC pretreatment with the anti-insulin affibody attenuated the lumbar sympathoexcitatory response to intracerebroventricular injection of insulin. Third, a hyperinsulinemic-euglycemic clamp increased lumbar, but not renal, SNA in animals that received ARC injection of a control affibody. However, this sympathoexcitatory response was absent in animals pretreated with the anti-insulin affibody in the ARC. Injection of the anti-insulin affibody in the adjacent ventromedial hypothalamus did not alter the sympathoexcitatory response to insulin. The ability of the anti-insulin affibody to prevent the sympathetic effects of insulin cannot be attributed to a general inactivation or nonspecific effect on ARC neurons as the affibody did not alter the sympathoexcitatory response to ARC disinhibition by gabazine. Collectively, these findings suggest that circulating insulin acts within the ARC to increase SNA.



1996 ◽  
Vol 270 (2) ◽  
pp. R342-R347 ◽  
Author(s):  
P. M. Smith ◽  
A. V. Ferguson

Extracellular single-unit recordings were obtained from area postrema neurons (AP), and peristimulus histograms were used to determine the effects of paraventricular nucleus (PVN) stimulation on these cells from anesthetized Sprague-Dawley rats. Of 91 AP cells tested, 30.8% responded to PVN stimulation with a short-latency (28.2 +/- 3.3 ms, mean +/- SE), short-duration (49.3 +/- 8.0 ms) excitation, whereas 8.6% were inhibited. In animals that had stimulation sites outside of PVN (non-PVN), only 4 of the 72 AP cells tested (5.6%) were influenced by stimulation. These excitatory effects of PVN stimulation on AP neurons were unaffected by V1-receptor blockade. Of 93 nucleus of the solitary tract (NTS) cells tested, 38.9% responded to PVN stimulation with a short-latency (18.5 +/- 2.4 ms), short-duration (48.8 +/- 9.6 ms) excitation and 22.2% with short-latency (20.75 +/- 4.1 ms), long-duration (204.4 +/- 44.9 ms) inhibitions. In contrast, non-PVN stimulation sites influenced only 19% of NTS neurons tested, all of which were excited. These data demonstrate that activation of PVN neurons elicits excitatory effects on the majority of AP neurons influenced. They further emphasize the potential significance of descending hypothalamic inputs in controlling neuronal activity in this circumventricular organ.



1995 ◽  
Vol 269 (5) ◽  
pp. R1174-R1178 ◽  
Author(s):  
J. L. Beverly ◽  
M. F. Beverly ◽  
M. M. Meguid

gamma-Aminobutyric acidergic (GABA) mechanisms in the ventral hypothalamus may be involved in counterregulatory responses to glucoprivic episodes. Microdialysis probes (1 mm) were placed into the ventromedial hypothalamus (VMH) or lateral hypothalamus (LHA) of male Sprague-Dawley rats 3.5 h before 2-deoxy-D-glucose (2-DG) administration (200 mg/kg i.v.). Probes were perfused (2 ml/min) with Ringer solution, and samples were collected every 10 min from 30 min before to 60 min after 2-DG. By 30 min after 2-DG, GABA concentration in VMH dialysate increased in a bimodal fashion to 204 +/- 36% (P < 0.01) of baseline, and GABA concentration in LHA dialysate decreased to 77 +/- 4% (P < 0.01) of baseline. The changes in dialysate GABA concentrations occurred concurrently with the animals eating and returned to baseline by 60 min. When animals were denied access to food after 2-DG, the decrease in LHA GABA was not apparent and VMH GABA remained approximately 15% above baseline at the end of the sample period. The results of the present study provide evidence that GABAergic systems in the ventral hypothalamus are responsive to alterations in glucose status.



1997 ◽  
Vol 272 (6) ◽  
pp. R1698-R1703 ◽  
Author(s):  
M. A. Allen ◽  
P. M. Smith ◽  
A. V. Ferguson

Adrenomedullin (ADM) circulates in the blood at concentrations comparable to other vasoactive peptides with established roles in cardiovascular regulation. Intravenously administered ADM produces a clear hypotensive effect, whereas intracerebroventricular microinjections result in increases in blood pressure (BP). Recently, we demonstrated that ADM influences neurons of the area postrema (AP), a central nervous system site implicated in cardiovascular control. However, to address directly the physiological significance of the actions of ADM at the AP, an in vivo microinjection study was undertaken. ADM, at two concentrations (1 and 10 microM), in volumes of 50, 100, and 200 nl, was microinjected into the AP or NTS of 21 urethan-anesthetized male Sprague-Dawley rats. Microinjection of 10 microM ADM (100 nl) resulted in significant transient (2-5 min) increases in BP [120 s area under the curve (AUC): 684.3 +/- 268.6 mmHg/s (P < 0.05)], and heart rate (HR) [AUC: 12.5 +/- 4.5 beats/min (P < 0.05)]. The lower concentration of ADM (1 microM) had no effect on either BP (179.1 +/- 143.6 mmHg/s) or HR (0.8 +/- 2.6 beats/min). ADM was also microinjected into the immediately adjacent nucleus of the solitary tract, where it was found to be without effect on either BP or HR. This study demonstrates, for the first time, a physiological role for ADM acting at a specific brain site, the AP, to produce significant cardiovascular responses.





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