Premium
Modulation of 5‐hydroxytryptamine‐induced head‐twitch response by drugs acting at GABA and related receptors
Author(s) -
Handley Sheila L.,
Singh Lakhbir
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb09461.x
Subject(s) - muscimol , picrotoxin , gabaa receptor , chemistry , bicuculline , gaba receptor antagonist , baclofen , long term potentiation , pharmacology , agonist , inverse agonist , receptor , gabab receptor , pentylenetetrazol , strychnine , biochemistry , anticonvulsant , biology , neuroscience , epilepsy
1 The effects of drugs acting at the γ‐aminobutyric acid (GABA) receptors and other chloride ionophore‐related sites have been studied for their ability to modulate the head‐twitch induced by 1–5‐hydroxytryptophan (5‐HTP) in the mouse. 2 The GABA a receptor agonists, muscimol, imidazoleacetic acid and 3‐aminopropanesulphonic acid, produced a dose‐related potentiation, while bicuculline inhibited the head‐twitch. The GABA b receptor agonist, baclofen, produced dose‐related inhibition. 3 Diazepam potentiated the head‐twitch while the ‘inverse’ benzodiazepine receptor agonist ethyl‐β‐carboline‐3‐carboxylate inhibited the head‐twitch. The antagonist Ro15‐1788 also produced inhibition. Ro05‐4864, a ligand for the benzodiazepine ‘acceptor’ site, potentiated the head‐twitch. 4 Pentobarbitone and pentylenetetrazol potentiated the 5‐HTP‐induced head‐twitch at low doses, changing to inhibition as the dose was increased. Picrotoxin in subconvulsant doses, produced only potentiation. More than one site may be involved in the action of these substances. 5 GABA, amino‐oxyacetic acid and 1–2‐4‐diaminobutyric acid inhibited the head‐twitch, while the GABA‐depletor, 3‐mercaptopropionic acid potentiated it. 6 Of all the agents tested, only muscimol produced head‐twitching when given alone. 7 It was concluded that both GABA a and GABA b receptors modulate the head‐twitch response to 5‐HTP.