I. J. Scherer, P. V. Holmes, R. B.S. Harris. The importance of corticosterone in mediating restraint-induced weight loss in rats. PHYSIOL BEHAV 00 (0) 000-000, 2010. Rats restrained for 3 h/day for 3d ays (RR) lose weight and do not return to the weight of non-restrained controls once restraint has ended. This study tested the importance of restraint-induced corticosterone release in mediating the change in body weight by injecting ADX rats with 2.0mg corticosterone/kg before each restraint to replicate the restraint-induced surge in circulating corticosterone. Restrained adrenalectomized (ADX) rats injected with corticosterone had the same initial weight loss as intact restrained rats, whereas corticosterone injection in non-restrained ADX rats and restraint of ADX rats injected with saline each produced only half as much initial weight loss. Sustained weight loss, measured for 14 days after the end of RR, was the same for restrained intact rats and restrained ADX rats injected with corticosterone whereas restrained ADX rats injected with saline achieved the same weight gain as their controls. Corticosterone injections had no effect on weight gain of non-restrained intact rats. In situ hybridization showed that corticotropin releasing factor (CRF) mRNA expression in the paraventricular nucleus of the hypothalamus (PVN) was increased by the same degree in ADX rats and restrained intact rats and was not modified by corticosterone injections. There was no significant effect of restraint, ADX or corticosterone injection on PVN arginine vasopressin (AVP) mRNA expression. These data indicate that a surge in corticosterone causes sustained weight loss in ADX rats through a mechanism that can be compensated for in intact rats and is independent of changes in PVN CRF or AVP mRNA expression.
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http://dx.doi.org/10.1016/j.physbeh.2010.11.014 | DOI Listing |
Alzheimers Dement
November 2024
BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Introduction: Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.
Methods: We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ, the pathogenic self-aggregating species of Aβ.
Results: MEDI1814 reduces free Aβ without impacting Aβ in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration.
Biochem Pharmacol
October 2024
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address:
Impaired activity of the hypothalamic-pituitary axis and reduced blood levels of glucocorticoids (GCs) are signature features of stress-related maladies. Recent evidence suggests a possible role of the tryptophan metabolite kynurenic acid (KYNA) in this context. Here we investigated possible causal relationships in adult male rats, using stress-induced fear discrimination as a translationally relevant behavioral outcome measure.
View Article and Find Full Text PDFMol Ther
April 2024
Q32 Bio, Waltham, MA 02451, USA. Electronic address:
Psychopharmacology (Berl)
October 2023
Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), 3801 University St, Montreal, QC, Canada.
Rationale: Positive allosteric modulation of metabotropic glutamate type 4 (mGlu) receptors is a promising strategy to alleviate parkinsonian disability and L-3,4-dihydroxyphenylalanine (L-DOPA) induced dyskinesia. ADX-88178 is a highly selective mGlu positive allosteric modulator (PAM) that previously enhanced the anti-parkinsonian action of L-DOPA in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease (PD).
Objectives: We sought to explore the effects of ADX-88178 on psychosis-like behaviours (PLBs) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset.
Front Physiol
May 2023
Multicenter Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.
Lactation overnutrition is a programming agent of energy metabolism, and litter size reduction leads to the early development of obesity, which persists until adulthood. Liver metabolism is disrupted by obesity, and increased levels of circulating glucocorticoids are pointed as a possible mediator for the obesity development, since bilateral adrenalectomy (ADX) can reduce obesity in different models of obesity. This study aimed to evaluate the effects of glucocorticoids on metabolic changes and liver lipogenesis and insulin pathway induced by lactation overnutrition.
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