Influence of 5-HT1A receptor antagonism on plus-maze behaviour in mice. II. WAY 100635, SDZ 216-525 and NAN-190.

To understand further the role of 5-hydroxytryptamine receptor subtype 1A (5-HT1A) mechanisms in anxiety, the behavioural effects of 5-HT1A receptor antagonists with different selectivity and intrinsic activity were examined using an ethological version of the murine elevated plus-maze test. WAY 100635 (0.03-9.0 mg/kg) produced a behavioural profile indicative of an anxiolyticlike effect, with an apparent bell-shaped dose-response relationship and increases in nonexploratory behaviours at the largest dose tested. SDZ 216-525 exerted a dose-dependent antianxiety action at doses of 0.05-0.8 mg/kg, with some loss of activity at 3.2 mg/kg. In contrast, smaller doses of NAN-190 had a significant effect, whereas higher doses (2.5-10.0 mg/kg) decreased locomotor activity and other active behaviours, a profile similar to that produced by the alpha1-adrenoceptor antagonist prazosin (2.5 mg/kg), which also inhibited open arm activity. Findings are discussed in relation to 5-HT1A receptor and alpha1-adrenoceptor antagonism and corresponding neurochemical changes. The results of the present series support the view that 5-HT1A receptor antagonists have therapeutic potential in the management of anxiety.