title: The γ-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens.
abstract: BACKGROUND
  Repeated morphine exposure can induce behavioral sensitization. There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. However, the effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear.
  
  
  METHODS
  We used morphine-induced behavioral sensitization model in rat to investigate the effects of baclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleus accumbens was evaluated using microdialysis assay in vivo.
  
  
  RESULTS
  The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhanced the locomotor activity following 4-day consecutive morphine administration and 3-day withdrawal period, which indicated the expression of morphine sensitization. In addition, chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development of morphine sensitization. It was also found that morphine challenge 3 days after repeated morphine administration produced a significant increase of extracellular dopamine release in nucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopamine release induced by morphine challenge.
  
  
  CONCLUSIONS
  Our results indicated that gamma-aminobutyric acid system plays an important role in the morphine sensitization in rat and suggested that behavioral sensitization is a promising model to study the mechanism underlying drug abuse.
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University, ChangChun, 130021, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Fu
authors.forename: Hongfa
authors.initials: H
authors.lastname: Yang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy / Q000517:prevention & control*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D000701:Analgesics, Opioid; D058786:GABA-B Receptor Agonists; D009020:Morphine; D001418:Baclofen; D004298:Dopamine