Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid states in the Wistar-Kyoto rat

Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed by antidepressants. Given that WKYs exhibit decreased sensitivity to some antidepressants and treatment-resistant depressed patients often show hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral and HPT hormonal responses of WKYs to altered thyroid status. "Euthyroid" WKYs had elevated basal plasma TSH and T₃ levels as compared to Wistars. Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased response latency in the open field test (OFT) of WKYs only. Administration of T₄ and T₃ suppressed plasma TSH equally in both strains. Wistars responded to increased T₃ levels with decreased response latency and increased activity in the OFT, but increased immobility in the forced swim test. In contrast, WKYs responded only to the high T₃ levels with decreased response latency in the OFT. These results suggest the existence of a decreased central nervous system sensitivity to thyroid hormones in WKYs that could be related to their depressive behavior.