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

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.

Awakenings in rats by ultrasounds: A new animal model for paradoxical kinesia.

Paradoxical kinesia refers to a sudden transient ability of akinetic patients to perform motor tasks they are otherwise unable to perform. The mechanisms underlying this phenomenon are unknown due a paucity of valid animal models that faithfully reproduce paradoxical kinesia. Here, in a first experiment, we present a new method to study paradoxical kinesia by "awakening" cataleptic rats through presenting appetitive 50-kHz ultrasonic vocalizations (USV), which are typical for social situations with positive valence, like juvenile play or sexual encounters ("rat laughter"). Rats received systemic haloperidol to induce catalepsy, which was assessed by means of the bar test. During that test, 50-kHz USV, time- and amplitude-matched white noise (NOISE), or background noise (BACKGROUND) were played back and compared to SILENCE. Every animal was exposed to all four acoustic stimuli in random order, with four independent groups of rats being tested. Only when exposed to playback of appetitive 50-kHz USV, the otherwise akinetic rats rapidly started to move efficiently. The acoustic control stimuli, in contrast, did not release rats from catalepsy, despite eliciting the auditory pinna reflex and head movements towards the sound source. Moreover, in a second experiment, playback of aversive 22-kHz USV and relevant acoustic control stimuli did also not significantly affect catalepsy time. Together, our animal model provides a completely new approach to study mechanisms of paradoxical kinesia, which might help to improve behavioral therapies for Parkinson's disease and other disorders, where akinetic or cataleptic states occur.