The GABAB agonist baclofen blocks the expression of sensitisation to the locomotor stimulant effect of amphetamine

The purpose of the present study was to test the possible influence of baclofen, a GABA(B) agonist, on the long-term sensitisation to amphetamine in rats. As expected, chronic amphetamine treatment (1.5 mg/kg i.p. daily for 10 days) led to an increased locomotor response to amphetamine (0.75 mg/kg i.p.), when the animals were challenged 20 days after the end of repeated treatment. Baclofen (2 mg/kg i.p.), administered before the test session, did not significantly modify the spontaneous locomotor activity of rats, but decreased the normal and, to a greater extent, the sensitised locomotor response to amphetamine; thus baclofen prevented the expression of sensitisation to amphetamine. Moreover a previous chronic treatment with baclofen (2 mg/kg i.p. daily for 10 days) attenuated the amphetamine-induced locomotor activity in sensitised, but not in control animals. This effect was observed 20 days after the last baclofen administration. In conclusion, the present results demonstrate that GABAB receptors play an important role in the expression of the sensitised behavioural response to amphetamine and further support a potential role of GABAB agonists in the treatment of psychostimulant addiction. (C) 2004 Lippincott Williams Wilkins.