Chronic (-)baclofen or CGP 36742 alters GABAB receptor sensitivity in rat brain and spinal cord.
Administration of the GABAB 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 microns 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 immunoreactivity or amino acid release was significantly reduced or increased in slices from rats pre-treated with the GABAB agonist or antagonist, respectively. These data suggest that functional responses to GABAB receptor activation in the mammalian central nervous system can be up- or down-regulated.
Malcangio
M
M
Department of Pharmacology, School of Pharmacy, London, UK.
Libri
V
V
Teoh
H
H
Constanti
A
A
Bowery
N G
NG
D000596:Amino Acids / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009833:Olfactory Pathways / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000032:analysis
D000596:Amino Acids; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D013373:Substance P; D001418:Baclofen