The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens

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.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.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.Repeated morphine administration can induce the neurochemical effects including mainly protein components and neurotransmission adaptations in the brain, which results in behavioral response underlying opioid dependence [1]. There are abundant reports have shown that locomotion sensitization has been suggested to mimic the brain changes that occur in the human addict [1-3], so it is intriguing animal model used to study neural mechanisms related to opioid dependence [4,5]. Morphine administration can produce a robust enhancement of locomotor activity in mice [6,7]. However, it induced dramatically an initial decrease and then an increase in locomotor activity in rats [1,8]. Hence, investigation of sensitization in rats may be interesting to better understand the potential mechanisms resulting in opioid dependence.There are increasing findings have demons