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

Background: Repeated morphine exposure can induce behavioral sensitization. There are evidences haveshown that central gamma-aminobutyric acid (GABA) system is involved in morphinedependence. However, the effect of a GABAB receptor agonist baclofen on morphineinducedbehavioral sensitization in rats is unclear. Methods: We used morphine-induced behavioral sensitization model in rat to investigate the effects ofbaclofen on behavioral sensitization. Moreover, dopamine release in the shell of the nucleusaccumbens was evaluated using microdialysis assay in vivo. Results: The present study demonstrated that morphine challenge (3 mg/kg, s.c.) obviously enhancedthe locomotor activity following 4-day consecutive morphine administration and 3-daywithdrawal period, which indicated the expression of morphine sensitization. In addition,chronic treatment with baclofen (2.5, 5 mg/kg) significantly inhibited the development ofmorphine sensitization. It was also found that morphine challenge 3 days after repeatedmorphine administration produced a significant increase of extracellular dopamine release innucleus accumbens. Furthermore, chronic treatment with baclofen decreased the dopaminerelease induced by morphine challenge. Conclusions: Our results indicated that gamma-aminobutyric acid system plays an important role in themorphine sensitization in rat and suggested that behavioral sensitization is a promising modelto study the mechanism underlying drug abuse.