Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system

Aricioglu F., Means A., Regunathan S.

EUROPEAN JOURNAL OF PHARMACOLOGY, cilt.504, sa.3, ss.191-197, 2004 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 504 Sayı: 3
  • Basım Tarihi: 2004
  • Doi Numarası: 10.1016/j.ejphar.2004.10.011
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.191-197
  • Anahtar Kelimeler: agmatine, morphine, dependence, withdrawal, cAMP, tyrosine hydroxylase, CLONIDINE-DISPLACING SUBSTANCE, NITRIC-OXIDE SYNTHASE, ALPHA(2)-ADRENOCEPTOR, TOLERANCE, NALOXONE, BRAIN, IMIDAZOLINE, WITHDRAWAL, ARGININE, AMINE
  • Marmara Üniversitesi Adresli: Evet

Özet

Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure. (C) 2004 Elsevier B.V. All rights reserved.