MODULATION OF PLUS-MAZE BEHAVIOR IN MICE BY THE PREFERENTIAL D-3-RECEPTOR AGONIST 7-OH-DPAT

Differences in the behavioural profiles of dopamine D-2 receptor antag onists (e.g., haloperidol vs. sulpiride) in animal models of anxiety h ave prompted speculation concerning the importance of their relative a ffinities for D-2-like receptor populations. In an initial attempt to investigate the involvement of D-3 receptors in anxiety, the present s tudy examined the effects of the preferential D-3-receptor agonist, (/-)7-OH-DPAT (0.01-10.0 mg/kg), on behaviours displayed by male mice i n the elevated plus-maze paradigm. An ethological approach incorporati ng measurement of a range of defensive acts and postures in addition t o conventional parameters was used to provide a comprehensive behaviou ral profile for the compound. Data analysis indicated a significant in crease in percentage of open-arm entries at 10 mg/kg and an altered te mporal distribution of behaviour at 1-10 mg/kg. Furthermore, risk-asse ssment measures (stretched attend postures, closed-arm returns) were d ose dependently reduced by drug treatment. Although these behavioural changes would be consistent with anxiety reduction, such an interpreta tion is negated by dose-dependent decreases in all active behaviours ( arm entries, rearing, and head-dipping) and by marked increases in ent ry latencies and nonexploratory behaviour at the highest dose tested. Overall, these effects are remarkably similar to those previously repo rted for quinpirole, suggesting either that D-2 and D-3 receptors exer t similar behavioural control or that the agents employed are sufficie ntly potent at D-2 receptors to prevent a resolution of D-2 and D-3 re sponses.