Risk Assessment Behaviour: Evaluation of Utility in the Study of 5-HT-Related Drugs in the Rat Elevated Plus-Maze Test

Abstract

The present study compared the effects of a wide range of 5-hydroxytryptamine (5-HT)-modulating and potential anxiolytic agents in the rat elevated plus-maze using spatiotemporal (i.e., open arm time and entries) and ethologically derived measures (i.e., risk assessment activities and directed exploration). The drugs used were 5-HT 1A receptor partial (buspirone and ipsapirone) and full (8-OH-DPAT and flesinoxan) agonists, mixed 5-HT 2A/2C receptor antagonists (ritanserin, ketanserin, mianserin, and pirenperone), selective 5-HT 3 receptor antagonists (ICS 205-930, MDL 72222, ondansetron, and ( RS)-zacopride), and selective (fluoxetine, fluvoxamine, and zimelidine) and nonselective (imipramine) 5-HT reuptake inhibitors. Only buspirone and mianserin produced effects indicative of an anxiolytic-like action on the spatiotemporal measures. However, all 5-HT 1A receptor ligands, as well as mianserin, ketanserin, ondansetron, and zacopride, decreased the number of aborted attempts at entry into open arms (risk assessment). In addition, buspirone, mianserin, and zacopride increased head-dipping (directed exploration). Among the 5-HT reuptake inhibitors, zimelidine reduced head-dipping and total entries. The present findings demonstrate that risk assessment responses are sensitive to the action of 5-HT 1A receptor ligands, but their modulation by drugs targetting 5-HT 2A, 5-HT 2C, and 5-HT 3 receptors was not convincingly established.