Changes in metabolic-related variables during chronic morphine treatment.
To reveal neuroendocrine/neurochemical changes that are responsible for the robust metabolic alterations seen during chronic morphine treatment we followed hormonal-, transcriptional- and behavioral changes during chronic morphine administration in adult male Wistar rats. Animals were implanted with increasing amount of slow release morphine tablets for 8 days. Morphine treated animals gain significantly less weight than placebo implanted controls. This weight loss is due to the dramatic decrease in the food intake and caloric efficiency in the first days of drug administration and to the lasting disregulated feeding pattern. Changes in feeding behavior included increase of diurnal and decrease of nocturnal feeding frequency in morphine treated rats. Significantly less leptin and insulin plasma levels were detected in morphine implanted animals than in placebo implanted controls, while adiponectin and ACTH concentration remain unchanged. Morphine treated rats display an increase of FosB/Delta FosB immunoreactivity at brain sites that have been implicated regulation of food intake and energy expenditure, including hypothalamic arcuate, paraventricular and ventromedial nuclei and in the lateral hypothalamic area as well as in the caudal brainstem. However, morphine-induced long-term metabolic alterations were not accompanied with any significant changes in the expression of anorexigenic neuropeptides POMC and CART in the hypothalamus and in the brainstem. The disregulated feeding pattern was not reflected in changes of orexin transcription, however, a compensatory upregulation was revealed in hypothalamic NPY expression.
Ferenczi
Szilamér
S
Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, P.O. Box 67, H-1450 Budapest, Hungary.
Núñez
Cristina
C
Pintér-Kübler
Bernadett
B
Földes
Anna
A
Martín
Fátima
F
Márkus
Vera Ladnyánszky
VL
Milanés
M Victoria
MV
Kovács
Krisztina J
KJ
D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D017931:DNA Primers; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D009020:Morphine / Q000494:pharmacology*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015430:Weight Gain / Q000187:drug effects
D000701:Analgesics, Opioid; D001786:Blood Glucose; D017931:DNA Primers; D006728:Hormones; D009479:Neuropeptides; D016760:Proto-Oncogene Proteins c-fos; D009020:Morphine