Plasticity of GABAB receptor in rat spinal cord detected by autoradiography.
Prolonged administration of (+/-)-baclofen induces tolerance to its antinociceptive effect in mice. In the present study we compare the effects of 21 days administration of (-)-baclofen or GABAB (gamma-aminobutyric acidB) receptor antagonists, with saline on the density of GABAB receptor binding sites in rat spinal cord using receptor autoradiography. Treatment with (-)-baclofen significantly reduced the number of silver grains (71%) whilst GABAB receptor antagonists, CGP 36742 (3-aminopropyl-n-butyl-phosphinic acid) and CGP 46381 (3-aminopropyl-cyclohexylmethylphosphinic acid), increased the grain count by 114% and 89%, respectively. These data indicate that GABAB receptors in the spinal cord can be influenced by prolonged administration of receptor ligands.
Malcangio
M
M
Department of Pharmacology, School of Pharmacy, London, UK.
Da Silva
H
H
Bowery
N G
NG
D000818:Animals; D001345:Autoradiography; D001418:Baclofen / Q000494:pharmacology*; D001665:Binding Sites; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D018080:Receptors, GABA-B; C086109:3-aminopropyl-cyclohexylmethylphosphinic acid; C079148:(3-aminopropyl)(n-butyl)phosphinic acid; D005680:gamma-Aminobutyric Acid; D001418:Baclofen