The GABAB-receptor antagonist, CGP 35348, antagonises gamma-hydroxybutyrate- and baclofen-induced alterations in locomotor activity and forebrain dopamine levels in mice.
Previous studies have shown that administration of gamma-hydroxybutyric acid (GHBA) or baclofen is associated with a decrease in locomotor activity as well as an increase of dopamine (DA) in brain. In the present study we analyse whether these actions are related to activation of GABAB-receptors utilising a GABAB-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 baclofen produced clear-cut increases in forebrain DA concentration. Also these effects were effectively antagonised by pretreatment with CGP 35348. Treatment with the GABAB-receptor antagonist alone did not influence the locomotor activity or brain DA concentration. These results indicate that the behaviourally depressive and DA increasing effects of GHBA and baclofen are mediated by activation of GABAB-receptors.
Nissbrandt
H
H
Department of Pharmacology, Göteborg University, Sweden.
Engberg
G
G
D000818:Animals; D001418:Baclofen / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D012978:Sodium Oxybate / Q000037:antagonists & inhibitors*
D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D012978:Sodium Oxybate; C066430:CGP 35348; D001418:Baclofen; D004298:Dopamine