Temporal differential adaptation of head-twitch and ear-scratch responses following administration of challenge doses of DOI.
Pharmacology, biochemistry, and behavior April 1995 DOI: 10.1016/0091-3057(94)00340-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical dose-response study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | DOI [(+/-)-1-(2 |
| Dose | 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 2.5 mg/kg |
| Duration | Challenge dose administered 48 h after first injection; repeated injections at 2-h intervals for 8 h |
| Measures | head-twitch response (HTR), ear-scratch response (ESR) |
| Key points | Initial DOI administration produced dose- and time-dependent increases in both head-twitch and ear-scratch responses in mice, with head-twitch responses appearing at 0.25 mg/kg and robust ear-scratch responses only at 1 mg/kg or higher. A 48-hour challenge with lower DOI doses (0.25 and 0.5 mg/kg) did not significantly affect the initial head-twitch scores. The authors attribute head-twitch to 5-HT2A receptor activation and ear-scratch probably to 5-HT2C receptor activation. |
Abstract
Previously, we reported that administration of the 5-HT2A/C receptor agonist, DOI [(+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane], can simultaneously produce the head-twitch response (HTR) and the ear-scratch response (ESR) in mice. Our recent studies have indicated that the HTR is a 5-HT2A receptor-mediated phenomenon, whereas the ESR is probably a 5-HT2C receptor-mediated event. The HTR and ESR exhibit subsensitivity to a challenge dose of DOI (2.5 mg/kg) administered 24 h after its acute or termination of its chronic (2.5 mg/kg, once daily for 13 days) administration. When the dose interval for the challenge dose of DOI was increased to 48 h, both the acute- and chronically treated mice exhibited a simultaneous supersensitive HTR response and a subsensitive ESR effect. The purpose of the present study was to investigate the dose-response effects of lower challenge doses of DOI 48 h following their respective first injections as well as determining the effects of repeated DOI injections at 2-h intervals for 8 h. Thus, in the present study, initial administration of DOI produced a dose- and time-dependent increase in the mean frequencies of both HTR and ESR. Significant HTRs were observed after administration of the lowest tested dose of DOI (0.25 mg/kg), whereas a robust frequency of ESR was only evident at 1 mg/kg or greater doses of DOI. A 48-h challenge administration of lower doses of DOI (0.25 and 0.5 mg/kg) did not significantly affect their respective first injection HTR scores.(ABSTRACT TRUNCATED AT 250 WORDS)