Date of Award
Master of Arts (MA)
College of Humanities and Social Sciences
Thesis Sponsor/Dissertation Chair/Project Chair
Alan L. Pehson
In the present study, we integrated the recent findings about rapid antidepressant action of ketamine and possible involvement of the serotonergic system, and 5-HT1B receptor in particular, in the pharmacodynamics of this drug. We modeled anhedonia, a prominent symptom of depression, using the progressive ratio test in Wistar Kyoto rats. This strain of rat is reportedly an endogenously stress-reactive organism that displays an anhedonia-like endophenotype. We hypothesized that Wistar-Kyoto rats’ performance would be impaired, compared to Wistar-Han controls, on this reward- and motivation- related task and that the treatment with 1o mg/kg ketamine 24 hours prior to testing will ameliorate this behavioral deficiency. To investigate whether the behavioral changes engendered by this treatment are modulated by the expression of 5-HT1B receptor in the nucleus accumbens, we performed ex vivo autoradiography in order to detect relative changes in 5-HT1B expression between experimental groups. We observed a significantly increased breakpoint in vehicle-treated Wistar-Kyoto rats, compared to Wistar-Han controls, while ketamine-treated Wistar-Kyoto rats were not significantly different from either control group. The levels of 5-HT1B expressions did not differ, regardless of the strain or treatment, suggesting that 5-HT1B receptor expression is not related to changes in hedonic states. In this thesis, we suggested possible interpretations and alternative explanations for obtained results, which are at odds with our expectations and with the general consensus in the literature. To highlight some possible methodological flaws of the operant conditioning tasks currently used in animal studies, we provided a more detailed review of the protocols employed in fixed ratio and progressive ratio tasks. In this thesis, we suggested an integrative theoretical model of ketamine pharmacodynamics, based on previous empirical studies in this area.
Fomin, Andriy, "The Effects of Ketamine on Performance in the Progressive Ratio Task and Nucleus Accumbens 5-HT1B Receptor Expression in Wistar-Kyoto Rats" (2023). Theses, Dissertations and Culminating Projects. 1328.
Available for download on Wednesday, June 25, 2025