Ultrasonic vocalizations as a measure of anhedonia in a rat model of endogenous depressionBanjac, Anamarija (Avtor) Živin, Marko (Vodja projekta) Zorović, Maja (Mentor) Wistar-Kyoto ratbrain-derived neurotrophic factorBDNFΔFosBanhedoniaaddictionAnhedonia is a core symptom of depression, defined as a diminished interest in stimuli or a diminished pleasure in response to stimuli that were previously perceived as rewarding. Current and novel antidepressant treatments notably underperform in alleviating anhedonia. The problem potentially stems from imprecise assessments of anhedonia that merge disrupted motivational (wanting) and consummatory (liking) aspects of reward experience. Therefore, precise experimental tools for the measurement of anhedonia in preclinical models are needed. To tackle this research gap, ultrasonic vocalizations (USVs) related to rewarding stimuli (amphetamine (AMPH)/ morphine (MORPH)) were measured and compared to standard measurements of anhedonia. Two rat lines were compared: the Wistar-Kyoto line (WKY, model of endogenous depression) and the Wistar line (W, control line). 50-kHz USVs were recorded in response to the first and last drug administration, and in anticipation of the last drug administration. Comparable behavioural measures were collected: drug-related locomotor activity, sucrose intake in the sucrose preference test (SPT) two times, and approach behaviour in the conditioned place preference (CPP) paradigm. Post-mortem, molecular markers for anhedonia (BDNF) and addiction (ΔFosB) were assessed in three brain regions involved in the reward circuit: prefrontal cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). All molecular data were assessed with adjusted band density acquired with Western Blot, count of mRNA-positive cells acquired by in-situ hybridization, and count of immunoreactive cells acquired by immunohistochemistry. Behaviourally, WKY rats emitted less 50-kHz USVs and crossed less distance in response to the first and last AMPH administration. WKY rats also showed divergence between USVs and locomotor responses during repeated treatment. Contrary to W rats, WKY rats exhibited sensitization of USVs. No differences between treatments were observed in the anticipatory situation. Sucrose intake in the SPT was reduced in the WKY line. No approach behaviour was observed in the CPP. BDNF levels were elevated in the WKY line for all three regions of interest. ΔFosB levels were elevated in the PFC of the WKY line. In conclusion, 50-kHz USVs showcase reduced reward response in the WKY line, evidenced by comparable behavioural measures and BDNF expression in the reward circuit.20262026-05-11 10:47:54Neznano182417sl