Emission of 50‑kHz ultrasonic vocalizations in dopamine-denervated rats treated with amphetamine: relevance to neurocircuitries involved in drug-mediated reward

Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to pleasurable stimuli, and USVs are increasingly being used to investigate the affective properties of drugs. Dopamine in the shell of the nucleus accumbens is instrumental in the emission of 50-kHz USVs, but little is known about how calling behavior is modulated by other brain regions that receive dopaminergic innervation. To clarify this issue, we evaluated calling behavior stimulated by repeated amphetamine administration in rats subjected to either bilateral or unilateral dopaminergic denervation with 6‑OHDA in the medial prefrontal cortex (mPFC), dorsolateral striatum (DLS), or medial forebrain bundle (MFB). Dopaminergic denervation in the PFC, DLS, or MFB only partially attenuated the development of 50-kHz USVs sensitization during repeated treatment with amphetamine. However, rats bearing a dopaminergic denervation in the mPFC emitted a low number of conditioned USVs upon re-exposure to the amphetamine-paired environment. Sensitization in ultrasonic calling and emission of 50-kHz USVs conditioned to an environment previously paired with drug administration have recently emerged as behavioral correlates of the motivational properties of drugs of abuse. Accordingly, the present results may provide new insight into the neurocircuitries involved in reward and motivation mediated by addictive drugs.