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.