Divergent acute and enduring changes in 50-kHz ultrasonic vocalizations in rats repeatedly treated with amphetamine and dopaminergic antagonists: new insights on the role of dopamine in calling behavior

Serra, Marcello

First

Investigation

;Costa, Giulia

Second

Formal Analysis

;Onaivi, Emmanuel

Penultimate

Writing - Review & Editing

;Simola, Nicola

Last

Conceptualization

2024-01-01

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Abstract

Background: Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to non-pharmacological and pharmacological stimuli, with addictive psychostimulants being the most effective drugs that elicit calling behavior in rats. Earlier investigations found that dopamine D1-like and D2-like receptors modulate the emission of 50-kHz USVs stimulated in rats by the acute administration of addictive psychostimulants. Conversely, information is lacking on how dopamine D1-like and D2-like receptors modulate calling behavior in rats that are repeatedly treated with addictive psychostimulants. Methods: We evaluated the emission of 50-kHz USVs in rats repeatedly treated (×5 on alternate days) with amphetamine (1 mg/kg, i.p.), either alone or together with: i) SCH 23390 (0.1-1 mg/kg, s.c.), a dopamine D1 receptor antagonist, ii) raclopride (0.3-1 mg/kg, s.c.), a selective dopamine D2 receptor antagonist, or iii) a combination of SCH 23390 and raclopride (0.1 + 0.3 mg/kg, s.c.). Calling behavior of rats was recorded following pharmacological treatment, as well as in response to the presentation of amphetamine-paired cues and to amphetamine challenge (both performed 7 days after treatment discontinuation). Results: Amphetamine-treated rats displayed a sensitized 50-kHz USV emission during repeated treatment, as well as marked calling behavior in response to amphetamine-paired cues and to amphetamine challenge. Antagonism of D1 or D2 receptors either significantly suppressed or attenuated the emission of 50-kHz USVs in amphetamine-treated rats, with a maximal effect after synergistic antagonism of both receptors. Conclusions: These results shed further light on how dopamine transmission modulates the emission of 50-kHz USVs in rats treated with psychoactive drugs.