Performance of a passive avoidance response is disrupted by compounds acting at 5HT(1A) receptors

In a previous study it was found that the anxiolytic drug buspirone and the related compounds gepirone and ipsapirone disrupted the performance of a passive avoidance response by rats. A similar effect was not produced by several other drugs including chlordiazepoxide, imipramine and haloperidol. In the present study the same procedure was used to investigate whether other compounds known to interact with serotonergic mechanisms would produce a similar effect. The 5HT(1A) agonists 8-OH-DPAT and MDL-72832 produced similar disruptions in the performance of a step-down passive avoidance response (i.e. decreased latencies), with 8-OH-DPAT giving rise to a bell-shaped dose-response curve. Neither ritanserin, a 5HT(2) antagonist, nor 1-PP, a metabolite of buspirone known to have alpha(2)-adrenoceptor antagonist properties, was active. Odansetron (GR38032F), a 5HT(3) antagonist, was active, although the magnitude of the effect was smaller than that seen with the 5HT(1A) agonists and was not clearly dose-related. In drug interaction experiments the effect of 8-OH-DPAT was completely eliminated after treatment with NAN-190 although NAN-190 itself increased step-down latencies. The effect of 8-OH-DPAT was also partially blocked by prazosin. Thus the performance of a step-down passive avoidance response is disrupted by a range of compounds known to be 5HT(1A) agonists but by few other drugs.