Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine

The GABA(B) agonist baclofen (BCF) has recently been reported to block the expression of sensitization to the locomotor effect of amphetamine (AMPH), and to reverse it after repeated administration. The present study was undertaken to investigate whether baclofen could also prevent the development of sensitization to the psychostimulant. Chronic AM PH treatment (1.5 mg/kg i.p. for 10 days) led to an increased locomotor response to AM PH (1.5 mg/kg) when the animals were challenged 3 and 30 days after the end of repeated treatment. Chronic co-administration of BCF (2 mg/kg, i.p.) and AMPH blocked the development of sensitization to the stimulant effect of AMPH. An ancillary experiment excluded that a 'state-dependency' hypothesis could account for the effect of baclofen. Furthermore, a previous repeated treatment with baclofen alone had no influence either on the acute AMPH effect or on the subsequent development of sensitization to AMPH. In conclusion, the results confirm that GABA(B) receptors play an important role in the acquisition of AMPH behavioural sensitization and further support a potential use of GABA(B) agonists in the treatment of psychostimulant addiction.