Effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of the GABAB receptor, CGP7930, on the development and expression of amphetamineinduced locomotor sensitization in rats

Abstract

BackgroundSeveral of the behavioral effects of amphetamine (AMPH) are mediated by an increase in dopamine neurotransmission in the nucleus accumbens. However, evidence shows that γ-aminobutyric acid B (GABAB) receptors are involved in the behavioral effects of psychostimulants, including AMPH. Here, we examined the effects of co-administration of the GABAB receptor agonist baclofen and a positive allosteric modulator of theGABAB receptor, CGP7930, on AMPH-induced locomotor sensitization. MethodsIn a series of experiments, we examined whether baclofen (2.0, 3.0 and 4.0mg/kg), CGP7930 (5.0, 10.0 and 20.0mg/kg), or co-administration of CGP7930 (5.0, 10.0 and 20.0mg/kg) with a lower dose of baclofen (2.0mg/kg) could prevent the development and expression of locomotor sensitization produced by AMPH (1.0mg/kg). ResultsThe results showed that baclofen treatment prevented both the development and expression of AMPH-induced locomotor sensitization in a dose-dependent manner. Furthermore, the positive allosteric modulator of the GABAB receptor, CGP7930, increased the effects of a lower dose of baclofen on AMPH-induced locomotor sensitization under both conditions. ConclusionThese data provide further evidence thatGABAB receptor ligands may modulate psychostimulant-induced behaviors.