Paradoxical kinesia induced by appetitive 50-kHz ultrasonic vocalizations in rats depends on glutamatergic mechanisms in the inferior colliculus

Abstract

Paradoxical kinesia is a sudden transient ability of akinetic patients to perform motor tasks they are otherwise unable to perform. This phenomenon is known to depend on the patient's emotional state and external stimuli. Paradoxical kinesia can be induced by appetitive 50-kHz ultrasonic vocalizations (USV) in rats displaying catalepsy following systemic haloperidol. We investigated the role of the inferior colliculus (IC) in paradoxical kinesia induced by 50-kHz USV, since the IC modulates haloperidol-induced catalepsy. We focused on glutamatergic and GABAergic neurotransmission, with male rats receiving intracollicular NMDA or the GABA receptor agonist diazepam 10 min before systemic haloperidol. Catalepsy time was assessed by means of the bar test, during which rats were exposed to playback of 50-kHz USV, white noise, and background noise. Our results show that playback of 50-kHz USV induced paradoxical kinesia by reducing haloperidol-induced catalepsy in rats which had received saline intracollicular microinjection. This paradoxical kinesia effect of 50-kHz USV playback on haloperidol-induced catalepsy was prevented by intracollicular NMDA administration. Although intracollicular diazepam microinjection potentiated haloperidol-induced catalepsy, it did not affect the response to 50-kHz USV playback. Together, NMDA receptor agonist suppressed the effectiveness of 50-kHz USV playback, whereas diazepam did not. These findings suggest that the IC is a key structure involved in paradoxical kinesia, with relevant processes being glutamatergic rather than GABAergic. Our approach thus appears useful for uncovering neural mechanisms of paradoxical kinesia and it might help identifying novel therapeutic targets for Parkinson's disease.