Modulation of 5‐hydroxytryptamine‐induced head‐twitch response by drugs acting at GABA and related receptors

Abstract

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. The GABAa receptor agonists, muscimol, imidazoleacetic acid and 3‐aminopropanesulphonic acid, produced a dose‐related potentiation, while bicuculline inhibited the head‐twitch. The GABAb receptor agonist, baclofen, produced dose‐related inhibition. 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. 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. GABA, amino‐oxyacetic acid and 1–2‐4‐diaminobutyric acid inhibited the head‐twitch, while the GABA‐depletor, 3‐mercaptopropionic acid potentiated it. Of all the agents tested, only muscimol produced head‐twitching when given alone. It was concluded that both GABAa and GABAb receptors modulate the head‐twitch response to 5‐HTP.

Diabetes inhibits the DOI-induced head-twitch response in mice

“…However, this speculation is also unlikely because there was no difference in the effect of DOI on the secretion of corticosterone between non-diabetic and diabetic mice. It has been reported that noradrenergic and GABA/benzodiazepine systems modulate the HTRs induced by 5-HT receptor agonists (Handley and Brown 1982;Handley and Singh 1985). We previously reported that diabetic mice showed the decreased turnover rates of noradrenaline in the frontal cortex (Kamei and Ohsawa 1997) and altered function of benzodiazepine receptors (Kamei and Ohsawa 2000).…”

Cross-species pharmacological characterization of the allylglycine seizure model in mice and larval zebrafish

“…For example, the disruption of GABAergic inhibition by a reverse GABA A receptor agonist (FG-7142) elicited c-fos expression changes in the orexin neuron hypothalamic network involved in stress and panic [82]. An important role for the GABAergic system has also been reported in the context of hallucinations [83]. Altogether, these mechanisms may possibly lead to the development of a multiindication drug discovery assay.…”

Regulation of 5-HT2A/C receptors and DOI-induced behaviors by protein kinase Cγ

“…For example, we have shown previously that PKCγ regulates ethanol-stimulated GABA A receptor function in cortex (Harris et al, 1995). It has been shown that GABAergic drugs modulate head twitch behavior in rodents, perhaps through interaction with 5-HT 2 receptors (Handley and Singh, 1985;Moser and Redfern, 1988;Tadano et al, 2001). Feng et al (2001) reported that activation of 5-HT 2 receptors in the prefrontal cortex of rats increased in vitro PKC activity toward GABA A receptor γ 2 subunits.…”