Influence of dopamine transmission in the medial prefrontal cortex and dorsal striatum on the emission of 50-kHz ultrasonic vocalizations in rats treated with amphetamine: Effects on drug-stimulated and conditioned calls

Rat ultrasonic vocalizations (USVs) of 50-kHz are increasingly being evaluated as a behavioral marker of the affective properties of drugs. Studies in amphetamine-treated rats have shown that activation of dopamine transmission in the nucleus accumbens (NAc) initiates the emission of 50-kHz USVs, but little is known on how dopamine transmission in other brain regions modulates the effects of drugs on calling behavior. To clarify this issue, we evaluated 50-kHz USV emissions in rats subjected to dopaminergic denervation of either the medial prefrontal cortex (mPFC) or the dorsal striatum (DS) and treated with amphetamine. Rats received amphetamine (1 mg/kg, i.p. × 5) on alternate days in a test cage; 7 days later, they were re-exposed to the test cage, to measure calling behavior that may reflect drug conditioning, and then challenged with amphetamine (1 mg/kg, i.p.). The numbers of total and categorized 50-kHz USVs emitted were evaluated, along with immunofluorescence for Zif-268 in the NAc. Dopamine-denervated and sham-operated rats displayed comparable patterns of calling behavior during amphetamine treatment and after amphetamine challenge. Conversely, rats that were dopamine-denervated in the mPFC, but not DS, emitted low numbers of 50-kHz USVs on test cage re-exposure. Finally, dopamine-denervated rats displayed a less marked increase in Zif-268-positive neurons in the NAc shell after amphetamine challenge, compared with sham-operated rats. These results may be relevant to identify the neuronal circuits that modulate 50-kHz USV emissions in rats treated with amphetamine, as well as the interplay between calling behavior and affective properties of drugs.