Abstract
BackgroundRepeated 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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
Highlights
IntroductionThere are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence
Repeated morphine exposure can induce behavioral sensitization
There are increasing findings have demonstrated that the mesolimbic dopamine (DA) system especially projecting from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens(NAc) is definitely involved in opioid dependence [9,10,11,12]
Summary
There are evidences have shown that central gamma-aminobutyric acid (GABA) system is involved in morphine dependence. The effect of a GABAB receptor agonist baclofen on morphine-induced behavioral sensitization in rats is unclear. There are increasing findings have demonstrated that the mesolimbic dopamine (DA) system especially projecting from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens(NAc) is definitely involved in opioid dependence [9,10,11,12]. Recent evidence has indicated that the GABAergic system is closely related to the mesolimbic dopaminergic system and involved in the modulation of addictive behavior [16,17,18,19]. Abundant convincing evidences have revealed that the GABAB receptor agonist can suppress many behavior changes induced by opioid and non-opioid [17]. Reports have indicated that gamma-aminobutyric acid transmission is more and more concerned
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