Involvement of noradrenaline in potentiation of the head-twitch response by GABA-related drugs.
The involvement of noradrenaline in the potentiation of head-twitching by drugs acting at GABA and related receptors has been examined in mice. The direct 5-HT agonist 5-methoxy-N,N-dimethyltryptamine was used to induce the head-twitch. The dopamine beta-oxidase inhibitor FLA-63 depleted whole brain noradrenaline by 90% and potentiated head-twitching when this was measured 4 h after injection. The GABAA-receptor agonists muscimol and 3-aminopropanesulphonic acid (3-APS), a low dose of pentobarbitone, diazepam and picrotoxin (PTX) potentiated control head-twitch rates but had no further effect when head-twitching had been potentiated by FLA-63. The potentiating action of FLA-63 was prevented by the beta-adrenoceptor antagonist metoprolol; the latter having no effect on control head-twitch rates. Muscimol and diazepam potentiation was examined and found to be blocked by metoprolol. The GABAB-receptor agonist baclofen reduced head-twitching. This was also prevented by FLA-63. The role of beta-adrenoceptors in modulating these actions of GABA-related drugs is discussed.
Singh
L
L
Heaton
J C
JC
Rea
P J
PJ
Handley
S L
SL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D002395:Catecholamines; D003975:Diazepam; D004298:Dopamine; D008732:Methoxydimethyltryptamines; D008790:Metoprolol; D009118:Muscimol; D009638:Norepinephrine; D010424:Pentobarbital; D010852:Picrotoxin; D013654:Taurine; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate