Biphasic effects of 5-HT agonism on impulsive responding are dissociable from effects on anxiety in the variable consecutive number task.

The serotonergic 5-HT receptor is known to be involved in both impulsivity and anxiety-related behavior. Although anxiety and impulsivity are different constructs, it has been shown that anxiogenesis can result in impulsiveness. It is therefore important to determine if the 5-HT receptor is involved in the commission of impulsive actions independent of its effects on anxiety. The 5-HT agonist 8-OH-DPAT (0.0125-0.1 mg/kg subcutaneous) increased impulsive action at low doses, but decreased it at higher doses, on the novel paced variable consecutive number with discriminative stimulus task (VCN). Neither the 5-HT antagonist WAY 100,635 (0.2-1.2 mg/kg subcutaneous), nor the noradrenergic antagonist and pharmacological stressor yohimbine (1-2 mg/kg intraperitoneal) altered measures of impulsivity. Stress induced by yohimbine was sufficient to produce anxiety-like behavior in the elevated zero maze, confirming that the VCN task is a selective assay of impulsive action that is not affected by anxiety. We hypothesize that the biphasic effect of 8-OH-DPAT is due to actions on presynaptic raphe 5-HT autoreceptors, and also postsynaptic 5-HT receptors. These results suggest that this receptor mediates impulsive action and that this is not secondary to its role in anxiety.