Differential effects of amphetamine on ultrasonic vocalizations and locomotor activity in a rat model of endogenous depression

The Wistar-Kyoto rat strain (WKY) is a model for treatment-resistant depression, exhibiting behaviors indicative of anhedonia. Although anhedonia is measured using the sucrose preference test (SPT), 50-kHz ultrasonic vocalizations (USVs) hold promise as a complementary assessment tool. This study aimed to detect whether 50-kHz USVs differ in the WKY rats compared to control Wistar (W) rats. First, WKY and W rats were compared for their basal 50-kHz calls. Then, rats were repeatedly treated with four administrations of either amphetamine (AMPH) or morphine (MORPH), and 50-kHz calls were recorded. In addition, the drug-evoked locomotor activity, sucrose consumption in the SPT, and the time spent in the drug- vs. saline-paired compartment in the conditioned place preference (CPP) test were collected. WKY rats emitted fewer basal calls and fewer calls following the first and the fourth AMPH administration. Contrary to controls, AMPH did not affect the number of calls in WKY rats following the first administration. WKY also displayed reduced AMPH-induced locomotor activity and sucrose consumption in the SPT. MORPH did not affect USVs or locomotion in either strain. The results highlight the benefits of 50-kHz calls as a complementary behavioral marker for assessing anhedonia in preclinical models of depression.