DOPAMINE D-1 AND D-2 RECEPTOR LIGANDS MODULATE THE BEHAVIOR OF MICE IN THE ELEVATED PLUS-MAZE

To further our understanding of the potential role of dopamine in mechanisms of anxiety, the effects fo four dopamine receptor ligands were examined in an ethological version of the murine elevated plus-maze test. The D-1 receptor partial agonist SKF 38393 (2.5-20.0 mg/kg), had minimal behavioural activity in this teat, whereas the selective D-1 receptor antagonist, SCH 23390 (0.025-0.2 mg/kg), had dose-dependent but behaviourally nonspecific effects. Quinpirole (0.0625-0.5 mg/kg), a D-2 receptor agonist, had no effects at low doses but severely disrupted locomotion and exploration at the highest doses tested. In marked contrast to the lack of effect or nonspecific effects seen with the other ligands tested, the D-2 receptor antagonist, sulpiride (2.5-20.0 mg/kg), produced an unambiguous anxiolytic-like profile under present test conditions. Although non of the doses tested adversely affected general activity, clear antianxiety effects were observed on both traditional and novel (i.e., risk assessment) behavioural measures. Data are discussed in relation to the relative importance D-1 and D-2 receptor mechanisms in plus-maze anxiety, and the need to further assess D-2 involvement through the use of more selective compounds.