Biphasic effects of 5-HT1A agonism on impulsive responding are dissociable from effects on anxiety in the variable consecutive number task
The serotonergic 5-HT1A 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-HT1A receptor is involved in the commission of impulsive actions independent of its effects on anxiety. The 5-HT1A 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-HT1A 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-HT1A autoreceptors, and also postsynaptic 5-HT1A receptors. These results suggest that this receptor mediates impulsive action and that this is not secondary to its role in anxiety.
Keywords5-HT1A receptors Anxiety Norepinephrine Operant Serotonin Stress
The authors thank Rachel Hardy, Nathan Pistory, Maeve Stewart, Taylor Proper, and Mikaela Whalen for assistance in conducting the studies.
MN, JJM, and PM conceived the design, MG, MN, PN, JJM, and PM conducted the research, MG, MN, PN analyzed the data, and MG, PN, and PM wrote the paper. All authors read and approved the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted (Edinboro University IACUC protocol #2017-0101). This article does not contain any studies with human participants performed by any of the authors.
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