The administration context does not influence the sensitization in the emission of 50-kHz ultrasonic vocalizations in rats treated with amphetamine in unfamiliar environments: Relevance to drug-induced modifications in the affective state

Costa G.

First

Conceptualization

;Todaro A.

Second

Investigation

;Marongiu L.

Penultimate

Investigation

;Simola N.

Last

Project Administration

2026-01-01

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Abstract

Rats emit 50-kHz ultrasonic vocalizations (USVs) in response to stimuli with positive emotional valence, including the administration of addictive/rewarding drugs. Dopaminergic psychostimulants are the drugs that most effectively stimulate the emission of 50-kHz USVs in rats, with repeated administration resulting in sensitized calling behavior. To further clarify the significance of amphetamine-induced sensitization in the emission of 50-kHz USVs, we evaluated how this behavioral response was affected by the administration context, which influences the affective/motivational properties of drugs. Rats were repeatedly treated in unfamiliar environments with amphetamine (1 mg/kg, i.p., × 5 on alternate odd days) spaced out with vehicle (i.p., × 5 on alternate even days), to evaluate the induction of sensitization in calling behavior. Part of the rats received amphetamine/vehicle in two physically different environments, whereas the remaining rats received both treatments in the same environment. Six days after treatment discontinuation, rats were first re-exposed to either the amphetamine-paired or vehicle-paired environment in drug-free conditions, to measure the emission of 50-kHz USVs on context re-exposure. Thereafter, rats were challenged in the same environment with amphetamine (1 mg/kg, i.p.), to evaluate the expression of sensitization in calling behavior. Induction and expression of sensitization in the emission of amphetamine-stimulated 50-kHz USVs occurred irrespective of the drug administration context, whereas no significant emission of 50-kHz USVs occurred on context re-exposure. These findings indicate that sensitization in the emission of 50-kHz USVs reveals effects of amphetamine on the affective/motivational state of rats that may not be influenced by the environment where the drug is experienced.