GABA(B) receptor inhibition causes locomotor stimulation in mice.
The present study investigated the effect of the administration of the GABA(B) receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid], CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid] and CGP 52432 (3-[[(3,4-dichlorophenyl)methyl]amino]propyl]diethoxymethyl)phosphinic acid), on spontaneous locomotor activity in mice. All drugs were acutely administered at the doses of 10 and 30 mg/kg (i.p.). The dose of 30 mg/kg of all drugs resulted in a significant stimulation of locomotor activity. The locomotor stimulation elicited by SCH 50911 was completely blocked by haloperidol (0.1 mg/kg, i.p.), suggesting that hyperactivity induced by blockade of the GABA(B) receptor is mediated by enhanced dopamine release. These results suggest the existence of a GABA(B) receptor-mediated tonic inhibition of dopamine neurons.
Colombo
G
G
C.N.R. Institute of Neurogenetics and Neuropharmacology, c/o Bernard B. Brodie Department of Neuroscience, University of Cagliari, S.S. 554, Km. 4.5, I-09042 Monserrato (CA), Italy. colomb@unica.it
Melis
S
S
Brunetti
G
G
Serra
S
S
Vacca
G
G
Carai
M A
MA
Gessa
G L
GL
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010721:Phosphinic Acids / Q000494:pharmacology
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D001596:Benzylamines; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D010721:Phosphinic Acids; C086109:3-aminopropyl-cyclohexylmethylphosphinic acid; C083008:CGP 52432; D006220:Haloperidol