Mean arterial blood pressure (MABP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), systemic vascular resistance index (SVRI), and central venous pressure (CVP) were measured in conscious, freely moving, sham-operated (SO) and chronically adrenalectomized (ADX) rats. After 3 weeks of ADX, the rats exhibited hypotension, tachycardia, and diminished SVI and CI. From 3 to 6 weeks after surgery, the HR decreased and SVRI increased. These changes were obscured when the same measurements were obtained in the same rats under enflurane anesthesia. Cardiovascular responses to an epinephrine (0.4 microgram/kg/min) infusion were measured in conscious SO and ADX rats. The magnitude of change from baseline to peak was similar in all groups, indicating that ADX did not alter the responsiveness of the cardiovascular system to epinephrine. The peak MABP response to epinephrine in ADX rats was significantly below that of SO control rats, suggesting that ADX impaired the ability of the cardiovascular system to maintain normal arterial blood pressure. No differences were found in plasma concentrations of Na+, K+, Cl-, PO4 =, or hematocrit that would help to explain the effect of long-term adrenalectomy. The data underscore the cardio-depressant effect of enflurane anesthesia, demonstrate the importance of a conscious rat model in studying the effects of ADX on the cardiovascular system, and emphasize that the full effects of ADX occur over a period of several weeks.
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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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