THE GABA(B)-RECEPTOR ANTAGONIST, CGP-35348, ANTAGONIZES GAMMA-HYDROXYBUTYRATE-INDUCED AND BACLOFEN-INDUCED ALTERATIONS IN LOCOMOTOR-ACTIVITY AND FOREBRAIN DOPAMINE LEVELS IN MICE
H. Nissbrandt et G. Engberg, THE GABA(B)-RECEPTOR ANTAGONIST, CGP-35348, ANTAGONIZES GAMMA-HYDROXYBUTYRATE-INDUCED AND BACLOFEN-INDUCED ALTERATIONS IN LOCOMOTOR-ACTIVITY AND FOREBRAIN DOPAMINE LEVELS IN MICE, Journal of neural transmission, 103(11), 1996, pp. 1255-1263
Previous studies have shown that administration of gamma-hydroxybutyri
c acid (GHBA) or baclofen is associated with a decrease in locomotor a
ctivity as well as an increase of dopamine (DA) in brain. In the prese
nt study we analyse whether these actions are related to activation of
GABA(B)-receptors utilising a GABA(B)-receptor antagonist, CGP 35348.
Administration of GHBA (200 or 800 mg/kg, i.p.) or baclofen (4 or 16
mg/kg, i.p.) induced a marked and dose-dependent decrease in locomotor
activity in mice, that was antagonised by pretreatment with CGP 35348
(400 mg/kg, i.p.). Treatment with the highest doses of GHBA and baclo
fen produced clear-cut increases in forebrain DA concentration. Also t
hese effects were effectively antagonised by pretreatment with CGP 353
48. Treatment with the GABA(B)-receptor antagonist alone did not influ
ence the locomotor activity or brain DA concentration. These results i
ndicate that the behaviourally depressive and DA increasing effects of
GHBA and baclofen are mediated by activation of GABA(B)-receptors.