Comparison of the effects of clonidine, rilmenidine, and guanfacine in the holeboard and elevated plusmaze. Drug Dev. Res. 15:405-414, 1988. The effects of clonidine, rilmenidine, and guanfacine were studied in the holeboard and elevated-plus maze tests in rats. In the holeboard test, clonidine had a profound effect on locomotor activity, significantly (P < 0.05) reducing this measure at all but one of the doses tested (0.005-0.25 mg/kg). In contrast, rilmenidine and guanfacine only markedly affected locomotor activity at 2.5 mg/kg or higher. The ED50's for locomotor activity were as follows: clonidine, 0.024 mg/kg; rilmenidine, 1.92 mgikg; and guanfacine, 1.65 mgikg. All three compounds also caused significant decreases in the number of head dips and time spent head-dipping. The effects of clonidine (0.005-0.25 mg/kg) and rilmenidine (0.25-1 0 mgikg) on the number of head-dips were significant (P < 0.01) at all doses and were dose dependent. The actions of guanfacine were similar, with all doses (0.1 25-5 mg/kg) differing significantly (P < 0.05) from the controls, except 1 mgikg. However, the time spent head-dipping was only decreased significantly (P < 0.05) by clonidine (0.005-0.25 mg/kg), rilmenidine (1, 5, and 10 mg/kg), and guanfacine (0.5-5.0 mgikg). In the elevated plus-maze, clonidine had no significant effect on the O/O number of entries made onto open arms, or the % of time spent on the open arms; rilrnenidine reduced the YO time spent on the