CHRONIC (-)BACLOFEN OR CGP-36742 ALTERS GABA(B) RECEPTOR SENSITIVITY IN RAT-BRAIN AND SPINAL-CORD

ADMINISTRATION Of the GABA, receptor agonist, (-)-baclofen 10 mg kg(-1), i.p. daily for 21 days to rats prevented (-)-baclofen-induced hyperpolarizing responses and synaptically-evoked late inhibitory potentials (IPSPs) in olfactory cortical neurones recorded intracellularly from 450 mu m brain slices. In contrast, pre-treatment with CGP 36742 induced a significant increase in (-)-baclofen-mediated post-synaptic responses and late IPSP amplitude. In the spinal cord, the potency of(-)-baclofen in inhibiting electrically-evoked substance P-like immuno-reactivity or amino acid release was significantly reduced or increased in slices from rats pre-treated with the GABA(B) agonist or antagonist, respectively. These data suggest that functional responses to GABA(B) receptor activation in the mammalian central nervous system can be up- or down-regulated.