Modulatory role of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), in morphine tolerance and dependence in mice
Küçük Resim Yok
Tarih
2010
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer Wien
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Elevated plasma asymmetric dimethylarginine (ADMA) levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that peripheral ADMA is an important contributor to opioid tolerance and dependence, by determining plasma ADMA levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to male mice, divided into groups of 3-, 6-, 9- and 10-day injection duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from carotid artery. The plasma levels of ADMA, symmetric dimethylarginine (SDMA), l-homoarginine and l-arginine in morphine-tolerant and -dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma ADMA and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous plasma ADMA, SDMA, l-homoarginine and l-arginine levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena.
Açıklama
Anahtar Kelimeler
Morphine, Tolerance, Dependence, Nitric Oxide, Asymmetric Dimethylarginine, L-Arginine Paradox, Opioid Tolerance, Antinociceptive Tolerance, Physical-Dependence, Abstinence Syndrome, Nervous-System, Receptor, Pain, Perspectives, Pharmacology
Kaynak
Journal Of Neural Transmission
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
117
Sayı
9
