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PubMed1995

Characteristics of BDNF-induced weight loss.

There is evidence that central infusion of brain-derived neurotrophic factor (BDNF) induces weight loss in rats. We have begun to investigate the physiological basis for BDNF-induced weight loss by assessing its relationship to (a) appetite, (b) serum indices of metabolic and renal toxicity, and (c) brain monoamine activity in areas associated with feeding or motor function. BDNF (0-6 microgram/day) was infused into the lateral ventricle (LV) of male Long-Evans rats for 14 days. Body weight and food intake were monitored throughout infusion and recovery periods. BDNF induced severe, dose-dependent appetite suppression and weight loss. Although appetite began to recover after the 10th infusion day, body weight had not returned to control values at the end of the recovery period. The weight loss observed in BDNF-infused rats was related to appetite suppression, since uninfused rats that were pair-fed to high dose BDNF-treated rats showed comparable weight loss. Despite severe weight loss, serum BUN, creatinine, thyroxine, glucose, and total protein were not affected by BDNF infusion. Striatal DO-PAC/DA was similarly unaffected by BDNF. In contrast, BDNF-infused rats showed a dose-dependent increase in hypothalamic 5-HIAA/5-HT that was not observed in pair-fed rats, suggesting that the observed increase in hypothalamic 5-HIAA/5-HT was a direct effect of BDNF infusion rather than a secondary effect of food restriction. These data suggest that BDNF may induce appetite suppression and weight loss through a central mechanism.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1976

Effect of an angiotensin antagonist, Sar1-Ala8-angiotensin II on physiological thirst.

Initially it was shown that infusion of Sar1-Ala8-angiotensin II (P113) into the third ventricle (50-100 mug/ml at 1.1 ml/hr) effectively abolished the large water intake induced 1-2 min after beginning an intracarotid infusion of angiotensin II at 800 ng/min which causes an unphysiologically high concentration of angiotensin II in cerebral arterial blood. Infusion of P113 (50-100 mug/ml at 1.1 ml/hr) into the third brain ventricle for 20 min prior to and during presentation of water to sheep after 48 hr water deprivation did not reduce water intake. Water intake associated with rapid food intake or carotid artery infusion of hypertonic NaC1 was similarly unaffected by intraventricular administration of P113. While high concentrations of angiotensin II are dipsogenic in sheep, these results cast doubt on a contributory role for angiotensin II in thirst caused by water depletion or rapid food intake in the sheep.

Angiotensin II↗

PubMed1995

Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats.

The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

Acetazolamide↗

PubMed2005

Alpha-synuclein-positive structures induced in leupeptin-infused rats.

Abnormal accumulation of alpha-synuclein is regarded as a key pathological step in a wide range of neurodegenerative processes, not only in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but also in multiple-system atrophy (MSA). Nevertheless, the mechanism of alpha-synuclein accumulation remains unclear. Leupeptin, a protease inhibitor, has been known to cause various neuropathological changes in vivo resembling those of aging or neurodegenerative processes in the human brain, including the accumulation of neuronal processes and neuronal cytoskeletal abnormalities leading to neurofibrillary tangle (NFT)-like formations. In the present study, we administered leupeptin into the rat ventricle and found that alpha-synuclein-positive structures appeared widely in the neuronal tissue, mainly in neuronal processes of the fimbria and alveus. Immunoelectron microscopic study revealed that alpha-synuclein immunoreactivity was located in the swollen axons of the fimbria and alveus, especially in the dilated presynaptic terminals. In addition colocalization of alpha-synuclein with ubiquitin was rarely observed in confocal laser-scan image. This is the first report of experimentally induced in vivo accumulation of alpha-synuclein in non-transgenic rodent brain injected with a well-characterized protease inhibitor by an infusion pump. The present finding suggests that the local accumulation of alpha-synuclein might be induced by the impaired metabolism of alpha-synuclein, which are likely related to lysosomal or ubiquitin-independent proteasomal systems.

Animals↗

PubMed2005

Sensitized effects of neuropeptide Y on multiple ingestive behaviors in P rats following ethanol abstinence.

Neuropeptide Y (NPY) suppresses ethanol drinking in alcohol-preferring (P) rats, an effect which is augmented following a single ethanol abstinence period. The present experiment tests both ethanol drinking and feeding in P rats following multiple abstinence periods. Female P rats had continuous access to 15% (v/v) ethanol and water for 6 weeks followed by 3 ethanol access cycles of 2 weeks with no ethanol and 2 weeks with ethanol. Following intracerebroventricular cannula implantation during the third period of ethanol abstinence, groups (n=12-13/dose) were infused with NPY (2.5, 5.0, 10.0 microg) or aCSF prior to ethanol reinstatement. Two additional groups (n=11-12/dose) were treated similarly except that ethanol access was uninterrupted, and they were infused with a single NPY dose (10.0 microg) or aCSF. NPY increased food intake in all groups, and this effect was greater following ethanol abstinence. NPY suppressed ethanol intake, and this suppression lasted longer (24 h post-infusion) in rats with a history of ethanol abstinence periods than rats with a history of continuous ethanol access (4 h post-infusion). These results confirm past findings and indicate that global dysregulation of brain NPY systems during ethanol abstinence may render P rats more sensitive to the behavioral effects of NPY.

Alcohol Drinking↗

PubMed2004

CCK-8 and PGE1: central effects on circadian body temperature and activity rhythms in rats.

Cholecystokinin-octapeptide (CCK-8) has been shown to possess an acute thermogenic and hyperthermic action when given intracerebroventricularly in slightly restrained rats. To substantiate the febrile nature of that hyperthermia freely moving animals should be used and together with body core temperature, at least one behavioral parameter, such as general activity, should also be recorded. In the present studies, Wistar rats (N=34) exposed to thermoneutral (26-28 degrees C) or cold (4 degrees C) ambient temperature and to a 12:12-h light/darkness schedule were infused intracerebroventricularly with CCK-8 or prostaglandin E1 (PGE1) for several days using ALZET minipump and changes in body core temperature and general activity were recorded by biotelemetry (Minimitter). In rats exposed to a thermoneutral ambient temperature, low doses of CCK-8 induced slight but significant rises of day minima of circadian body temperature rhythm (CBTR) and with a high dose (1 microg/h) of the peptide--infused either at thermoneutrality or during cold exposure--an increase of acrometron could also be recorded. All of these changes were observed only during the first 2-4 days of 7-day-long infusions. Intracerebroventricular infusion of PGE1 administered at thermoneutrality in a dose of 1 microg/h for 7 days induced a marked rise in body core temperature with a disappearance of CBTR in some rats for 2-3 days or with rises of day minima/acrometron in others. General activity--running parallel with CBTR in periods without infusions--tended to be decreased when core temperature rose during the first couple of days of intracerebroventricular infusion of higher doses of CCK-8 or of PGE1. The decreased general activity--one component of sickness behavior--together with an increased body core temperature found in the present study, supports the view that they are components of a genuine fever induced by the central effect of the two mediators used.

Alprostadil↗

PubMed2006

Does central nitric oxide elicit pulmonary hypertension in conscious rats?

The mechanisms involved in the pathogenesis of pulmonary arterial hypertension (PAH) remain unclear. Nitric oxide (NO) centrally attenuates sympathetic outflow and, therefore, may chronically modulate pulmonary arterial pressure (PAP), especially during the development of chronic hypoxia-induced PAH. To test this hypothesis, 20 male Sprague-Dawley rats (B.W. approximately 200-320 g) were chronically implanted with a telemetric transmitter for the continuous measurement of PAP, and an osmotic pump for intracerebroventricular (i.c.v.) administration of either aCSF (control), L-NAME (150 microg/kg/day) or the NO-donor, SIN-1 (100 microg/kg/day). Rats spent 7 days in normoxia, and then 14 days in hypoxia (CH=12% O2). In normoxia, exogenous NO elevated PAP by approximately 64%, although this increase in PAP could be prevented by isoproterenol (200 mug/kg). PAH occurred in all rats following 14 days of hypoxia. L-NAME did not alter baseline MPAP or the physiological responses to hypoxia. Our results suggest that central NO increases MPAP, although the mechanisms involved remain to be fully elucidated.

Adrenergic beta-Agonists↗

PubMed2000

Prolonged intracerebroventricular infusion of neurosteroids affects cognitive performances in the mouse.

The effects of prolonged intracerebroventricular (i.c.v.) steroid infusions on memory performances (Y-maze arm discrimination test) and on neurosteroids brain levels were studied in young adult male mice. The Y-maze test consisted of two trials separated by a time interval. In the first trial, one arm of the maze (subsequently called novel arm) was closed, and mice were allowed to visit the two accessible arms. After a short 2-h intertrial interval (ITI), control mice explored preferentially the novel arm, whereas with a longer 6-h ITI, they did not remember the location of the novel arm and performed at random level (33% of time spent in each arm). Using a 2-h ITI, allopregnanolone (THPROG, 0.5 and 1 ng/h) decreased memory performances to random level after 3 and 6 days of infusion. Conversely, with a 6-h ITI, pregnenolone sulfate (PREG S, 10, 50, and 100 ng/h) significantly increased memory performances after 3 days, but only the smallest dose was still effective after 6 days. THPROG infusion (1 ng/h) increased the forebrain concentration of 5alpha-dihydroprogesterone (DHPROG) and tended to increase its own level. PREG S administration (10 ng/h) increased its own concentration and tended to increase those of pregnenolone (PREG) and of further metabolites. In conclusion, the memory-enhancing effects of PREG S and the inhibitory ones of THPROG have been confirmed. A persistent, however moderate, increase of PREG S brain concentration might be of interest for the treatment of amnesic deficits.

5-alpha-Dihydroprogesterone↗

PubMed2002

Changes of GABA(A) receptor binding and subunit mRNA level in rat brain by infusion of NOS inhibitor.

In the present study, we have investigated the effects of prolonged inhibition of nitric oxide synthase (NOS) by infusion of NOS inhibitor, L-nitroarginine, to examine the pentobarbital-induced sleep, modulation of GABA(A) receptor binding, and GABA(A) receptor subunit mRNA level in rat brain. Pre-treatment with L-nitroarginine 30 min before pentobarbital treatment (60 mg/kg, i.p.) significantly increased the duration of sleep in rats. However, the duration of pentobarbital-induced sleep was shortened by the prolonged infusion of L-nitroarginine into ventricle. We have investigated the effect of NOS inhibitor on GABA(A) receptor binding characteristics in discrete areas of brain regions by using autoradiographic and in situ hybridization techniques. Rats were infused with L-nitroarginine (10, 100 pmol/10 microl/h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps. The levels of [(3)H]muscimol and [(3)H]flunitrazepam binding were markedly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, there was no change in the level of [(35)S]TBPS binding. The levels of beta2-subunit were elevated in the cortex, brainstem, and cerebellar granule layers. By contrast, the levels of beta3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in L-nitroarginine-infused rats. Following L-nitroarginine treatment, the levels of alpha6- and delta-subunits which were strictly localized to the cerebellum, were not changed in the cerebellar granule layer. These results show that the prolonged inhibition of NOS by L-nitroarginine-infusion markedly elevates [(3)H]muscimol and [(3)H]flunitrazepam binding throughout the brain, and alters GABA(A) receptor subunit mRNA levels in different directions. Chronic inhibition of NO generation has differential effects on the various expressions of GABA(A) receptor subunits. These suggest the involvement of different regulatory mechanisms for the NO-induced expression of GABA(A) receptor.

Animals↗

PubMed1999

Brain-IL-1beta induces local inflammation but systemic anti-inflammatory response through stimulation of both hypothalamic-pituitary-adrenal axis and sympathetic nervous system.

It is well established that systemic inflammation induces a counter-regulatory anti-inflammatory response particularly resulting in deactivation of monocytes/macrophages. However, recently we demonstrated a systemic anti-inflammatory response without preceding signs of systemic inflammation in patients with brain injury/surgery and release of cytokines into the cerebrospinal fluid (CSF). In order to analyze the mechanisms and pathways of systemic immunodepression resulting from sterile cerebral inflammation we established an animal model using continuous intra-cerebroventricular (i.c.v.) or intra-hypothalamic (i.h.) infusion of rat recombinant (rr) tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta for 48 h. Controls received intra-venous (i.v.) cytokine administration. Interestingly, i.c.v. and i.h. infusion of IL-1beta but not TNF-alpha produced distinct signs of central nervous system (CNS) inflammation. Correspondingly, i.c.v. infusion of IL-1beta particularly diminished the TNF-alpha but increased the IL-10 concentration in whole blood cultures after endotoxin stimulation. All parameters normalized within 48 h after termination of the infusion. Blocking the hypothalamic-pituitary-adrenal (HPA) axis by hypophysectomy (HPX) led to complete recovery of the diminished TNF-alpha concentration and temporarily inhibited the IL-10 increase. Blocking the sympathetic nervous system (SNS) transmission by application of the beta2-adrenoreceptor antagonist propranolol not only inhibited the increase but further downregulated the endotoxin induced IL-10 concentration in the media of whole blood cell cultures, whereas the TNF-alpha decrease was only partially prevented. Interestingly, HPX and propranolol also diminished the cell invasion into the CSF. In summary, activation of both the HPA axis and the SNS plays an important role in systemic anti-inflammatory response resulting from cytokines in brain and cerebral inflammation.

Animals↗

PubMed1998

Downregulation of brain mineralocorticoid and glucocorticoid receptor by antisense oligodeoxynucleotide treatment fails to alter spatial navigation in rats.

Adult male Brown Norway rats were long-term intracerebroventricularly (i.c.v.) infused with antisense oligodeoxynucleotides (18-mer, double endcapped phosphorothioate protected) targeting either mineralocorticoid or glucocorticoid receptor mRNA, or received the respective mixed bases sequence or vehicle. Mineralocorticoid receptor-mixed bases and glucocorticoid receptor-mixed bases oligodeoxynucleotide infusion (1 microg/0.5 microl/h) over a time period of seven days did not alter hippocampal mineralocorticoid receptor and glucocorticoid receptor binding when compared to vehicle treatment. In contrast, i.c.v. administration of mineralocorticoid receptor, as well as glucocorticoid receptor-antisense over the same time period resulted in a significantly reduced binding of mineralocorticoid receptor and glucocorticoid receptor in the hippocampus [mineralocorticoid receptor-antisense group approx. 72% of mineralocorticoid receptor-mixed bases and vehicle groups (100%); glucocorticoid receptor antisense group approx. 77% of glucocorticoid receptor-mixed bases and vehicle]. The specificity of these antisense effects is indicated by the finding that rats treated with mineralocorticoid receptor-antisense did not show any changes in glucocorticoid receptor and vice versa. Animals treated according to this infusion protocol and tested in the Morris water maze for their spatial navigation abilities failed to show significant differences among the groups. These data indicate that a reduction of hippocampal mineralocorticoid receptor or glucocorticoid receptor binding capacity by 20-30% does not interfere with spatial navigation.

Animals↗

PubMed1996

An approach to study molecular mechanisms involved in cytokine-induced anorexia.

Cytokines are released during pathophysiological processes. Cytokines (e.g., interleukin-1 beta or IL-1 beta) induce neurological manifestations including anorexia. Here, we show an integrative approach to investigate the cellular and molecular basis of cytokine-induced anorexia. In this approach: (1) the chronic intracerebroventricular (icv) microinfusion (via osmotic minipumps) of cytokines, at doses that will yield estimated pathophysiological concentrations reported in the cerebrospinal fluid, is used. (2) General and computerized behavioral monitoring characterizes the microstructure of behavioral modifications induced by a cytokine, and the time course for cytokine action. (3) Brain regions and subregions (nuclei/areas) from animals exhibiting significant anorexia in response to cytokine(s) are dissected, and RNA and protein are isolated. (4) The profile of cytokine subsystems (ligands, receptors, endogenous inhibitors; for example, IL-1 alpha and beta, IL-1 receptor types I and II, and IL-1 receptor antagonist) is characterized in the same brain samples with polymerase chain reaction, sensitive RNase protection assays and immunoblots. (5) The relationship between changes in cytokine subsystems at the molecular level and cytokine-induced anorexia within an animal is determined, and the general profile is analyzed with statistical methods. This approach is also pertinent to study neurotransmitter and neuropeptide profiles, and cytokine-cytokine, cytokine-neuropeptide and cytokine-neurotransmitter interactions in vivo. The results show that this integrative and novel strategy can be used to study the molecular basis of anorexia and other neurological manifestations (e.g., fever, sleep changes) induced by cytokines.

Animals↗

PubMed1998

Effect of infusion of vasoactive intestinal peptide (VIP)-antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats.

We examined the effect of the infusion of a vasoactive intestinal peptide (VIP) antisense oligodeoxynucleotide into the third cerebral ventricle above the hypothalamic suprachiasmatic nucleus (SCN) using osmotic minipump for 3 days (0.2 nmol/ml per h) on the hyperglycemic response to intracerebroventricular injection of 2-deoxy-D-glucose (2DG) (80 micromol) in rats. After the infusion of the VIP antisense the inhibition of VIP expression in the SCN was observed in association with suppressions of the hyperglycemia, hyperglucagonemia and relative hypoinsulinemia due to the 2DG injection. Furthermore, additional intracranial injection of VIP (4 nmol) restored these responses to the 2DG injection in rats treated with the VIP antisense. These findings suggest that VIP neurons in the SCN are involved in the regulation of glucose metabolism.

Animals↗

PubMed2000

Intracavitary administration of amphotericin B in the treatment of cerebral aspergillosis in a non immune-compromised patient: case report and review of the literature.

A 24-year-old man presented with cerebral aspergillus fungal granuloma involving the left frontal region secondary to pulmonary aspergillosis. He was otherwise healthy with no evidence of immune-suppression. Because of poor penetration of amphotericin B into the brain and cerebrospinal fluid (CSF), this patient was treated by a combination of systemic and local therapy in addition to surgical excision resulting in a cure with follow up for more than three years. This form of treatment produced no untoward long-term side effects or neurological sequel. On review of the literature on aspergillosis of the central nervous system (CNS), we found that six patients, including the present case, have been reported who survived longer than 1 year; their treatment included local administration of antifungal agent in the abscess cavity or into cerebral ventricles in order to control this devastating, treatment-resistant pathological fungal infection.

Adult↗

PubMed1998

Effects of diaspirin cross-linked haemoglobin on post-traumatic cerebral perfusion pressure and blood flow in a rodent model of diffuse brain injury.

Diaspirin cross-linked haemoglobin (DCLHb) is a new oxygen carrying blood substitute with vasoactive properties. Vasoactive properties may be mediated via high affinity binding of nitric oxide by the haem moiety. Using a rodent model of head injury combined with ischaemia, we studied the effects of DCLHb on cerebral blood flow (CBF) and intracranial pressure (ICP). Twenty anaesthetized rats were allocated randomly to receive treatment with DCLHb 400 mg kg-1 i.v. or placebo (oncotically matched plasma protein substitute 4.5% i.v.). To produce diffusely increased ICP, after a severe weight drop injury, all animals underwent a 30-min period of bilateral carotid ligation combined with a period of induced hypotension. After reperfusion, DCLHb or placebo was infused and the animals instrumented for measurement of intraventricular ICP and CBF in the region of the sensorimotor cortex using the hydrogen clearance technique. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP) (CPP = MAP - ICP) and CBF were measured 4 h after injury in all animals. DCLHb significantly reduced ICP from mean 13 (SEM 2) to 3 (1) mm Hg (P < 0.001), increased CPP from 52 (8) to 95 (6) mm Hg (P < 0.001) and increased CBF from 21 (2) to 29 (2) ml 100 g-1 min-1 (P = 0.032). We conclude that DCLHb improved CPP without a reduction in CBF in a rodent model of post-traumatic brain swelling.

Animals↗

PubMed2002

Aldosterone acts on the kidney, not the brain, to cause mineralocorticoid hypertension in sheep.

OBJECTIVE: To determine the extent to which mineralocortioid hypertension depends on a direct action of aldosterone on the kidney or on the brain. METHODS: Studies were performed in conscious sheep that were previously uninephrectomized, implanted with silastic cannulae in the renal artery of the remaining kidney, and had guide tubes implanted over the lateral cerebral ventricles. The effect of aldosterone, infused either intrarenally (i.r.; 2 microg/h) or intravenously (i.v.; 2 and 10 microg/h) for 10 days (n = 5), on arterial pressure and fluid and electrolyte balance was determined. The i.r. (2 microg/h) and i.v. (10 microg/h) doses were calculated to give similar intrarenal concentrations of aldosterone. In a further study, the effect of intracerebroventricular (i.c.v.) infusion of aldosterone (2 microg/h for 21 days) on arterial pressure was examined (n = 5). RESULTS: Infusion of aldosterone caused a progressive increase in mean arterial pressure from 83 +/- 3 mmHg to a maximum of 100 +/- 4 mmHg (P < 0.001) with 2 microg/h i.r. and from 84 +/- 3 mmHg to a maximum of 104 +/- 4 mmHg (P < 0.001) with 10 microg/h i.v., both by day 7. With both infusions there were similar increases in plasma [Na+] and decreases in plasma [K+] and total protein concentration (P < 0.05) between days 3 and 5; these were maintained throughout the infusion. There were no significant changes with i.v. aldosterone (2 microg/h). Long-term i.c.v. infusion of aldosterone (2 microg/h for 21 days) caused no change in arterial pressure. CONCLUSIONS: In conscious sheep the hypertensive response to aldosterone resulted from an action on the kidney, with no evidence for a direct action on the brain.

Aldosterone↗

PubMed1994

Effect of hemicholinium-3 on the hypothalamic concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase-stimulating substance.

Hypothalamus and plasma of salt-loaded rats, spontaneously hypertensive rats (SHR), and hypertensive reduced renal mass rats (RRM), and the plasma of patients with essential hypertension and of Milan hypertensive rats contain an increased concentration of a cytochemically detectable glucose-6-phosphate dehydrogenase (G6PD)-stimulating substance that has properties similar to that of a possible choline derivative di-methyl methylene immonium ion. Intracerebroventricular (i.c.v.) administration of hemicholinium-3 (HC-3) selectively blocks high-affinity neuronal choline uptake, inhibits brain acetylcholine (ACh) synthesis, and decreases arterial pressure in SHR through an inhibiting effect on hypothalamic cholinergic function. The experiments were performed to study the effect of centrally administered HC-3 on the content of the cytochemically detectable cholinelike substance in hypothalamus and plasma of SHR. HC-3 or saline was infused into the lateral cerebral ventricle for 6 days with a minipump in 14 SHR. On day 7, the hypothalamic and plasma concentration of the cytochemically detectable substance was significantly reduced in rats that received HC-3. The hypothalamic concentration was 225 +/- 95.6 x 10(8) G6PD U per hypothalamus (range 38.2-775) in SHR that received saline and 1.037 +/- 0.45 x 10(8) G6PD U (range 0.112-3.61) (p < 0.05) in SHR that received HC-3. The respective plasma concentrations were 284.9 +/- 26 U/ml (range 192-374) and 72.7 +/- 14.7 U/ml (range 24-119) (p < 0.05). The findings are consistent with the physicochemical evidence, which suggests that the cytochemically detectable substance is a choline derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed2001

Central leptin infusion attenuates the cardiovascular and metabolic effects of fasting in rats.

The role of reduced leptin signaling in the regulation of cardiovascular responses to negative energy balance is not known. We tested the hypothesis that central infusion of leptin would attenuate the cardiovascular and metabolic responses to fasting. Male Sprague-Dawley rats, instrumented with telemetry devices and intracerebroventricular cannulas, were housed in metabolic chambers for continuous (24 hours) measurement of dark-phase (active) and light-phase (inactive) mean arterial pressure, heart rate, oxygen consumption, and respiratory quotient. Rats received central infusions of either saline (0.5 microL/h) or leptin (42 ng/h) for 6 days through osmotic pumps and were either fed ad libitum or were fasted for 48 hours followed by refeeding for 4 days. In ad lib animals, continuous intracerebroventricular leptin infusion significantly reduced caloric intake, body weight, and respiratory quotient compared with saline controls while having no effect on mean arterial pressure or heart rate. Fasting reduced mean arterial pressure, heart rate, oxygen consumption, and respiratory quotient in rats receiving saline infusions. Fasting-induced reductions in mean arterial pressure were specific to the active phase and were not attenuated by central leptin infusion. In contrast, intracerebroventricular leptin, at a dose that had no cardiovascular effects in ad lib control animals, completely prevented fasting-induced decreases in light-phase heart rate and oxygen consumption and blunted fasting-induced reductions in dark-phase heart rate and oxygen consumption. The results are consistent with the hypothesis that reductions in central leptin signaling contribute to the integrated cardiovascular and metabolic responses to acute caloric deprivation.

Animals↗