Rationale Gaboxadol is a selective agonist at GABAA receptors that contain α4-δ subunits, and it produces anxiolytic and sedative effects. Although adverse effects preclude its clinical use, its mechanism of action suggests that those receptors might provide novel therapeutic targets, particularly for modulators of those GABAA-receptor subtypes, by retaining therapeutic effects of gaboxadol and not adverse effects. Objectives The current study compared discriminative stimulus effects of gaboxadol with those of modulators acting at GABAA receptors containing α4-δ subunits. Materials Eight rats discriminated 5.6 mg/kg gaboxadol from vehicle while responding under a fixed-ratio 10 schedule for food. Modulators acting at GABAA receptors containing α4-δ subunits (pregnanolone, ethanol, flumazenil) and receptors that do not contain those subunits (midazolam) were studied alone; pregnanolone and ethanol were also combined with gaboxadol. In addition, gaboxadol was studied in separate groups discriminating 0.32 mg/kg midazolam, 3.2 mg/kg pregnanolone, or 0.75 g/kg ethanol from vehicle. Results Gaboxadol produced ≥80% gaboxadol-lever responding and did not alter rates. No other drug produced, on average, ≥80% drug-lever responding up to doses that decreased rates, although 1.78 mg/kg midazolam produced 32% gaboxadol-lever responding. Ethanol and pregnanolone did not enhance the effects of gaboxadol. Rats discriminating midazolam, pregnanolone or ethanol from vehicle responded predominantly on the vehicle lever after receiving gaboxadol. Conclusions Drugs that modulate GABAA receptors containing α4-δ subunits neither mimicked nor enhanced the discriminative stimulus effects of gaboxadol, indicating that at least some effects of gaboxadol are not shared with modulators of that GABAA-receptor subtype.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.