Different behavioural profiles of the R(+)- and S(-)-enantiomers of 8-hydroxy-2-(di-n-propylamino) tetralin in the murine elevated plus-maze.
(=) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been the most widely used pharmacological tool in research on 5-HT(1A) receptor function. In the present study, the behavioural effects of 8-OH-DPAT entantiomers were compared using an ethological version of the murine elevated plus-maze test. Subcutaneous pretreatment (-20min) with R(+)-8-OH-DPAT (0.03-1.0mg/kg) produced a pronounced; and dose-dependent behavioural suppression (decreased open/closed/total arm entries and increased nonexploratory behaviours). In contrast, over the same dose range, S(-)-8-OH-DPAT reduced several ethological indices of anxiety without altering the majority of conventional parameters or general activity levels, e.g. arm entries and per cent time measures, as well as head dipping. Findings are discussed in relation to differences in the intrinsic activity of 8-OH-DPAT isomers at 5-HT(1A) sites and the putative role of these receptors in anxiety-related processes. The differential behavioural profiles of 8-OH-DPAT enantiomers suggest that racemic 8-OH-DPAT may not be an ideal tool for research on the behavioural pharmacology of 5-HT(1A) receptors.
Ethopharmacology Laboratory, Department of Psychology, University of Leeds, LS2 9JT, UK.
B J
BJ
Cao
R J
RJ
Rodgers