Abstract
RationaleIn rodents, acute haloperidol treatment induces psychomotor impairments known as catalepsy, which models akinesia in humans and is characterized as an animal model of acute Parkinsonism, whereas sub-chronic haloperidol reduces exploratory behavior, which resembles bradykinesia. Haloperidol-induced catalepsy in rats can be ameliorated by playback of 50-kHz ultrasonic vocalizations (USV), an emotionally and motivationally relevant appetitive auditory stimulus, representing an animal model of paradoxical kinesia. In a condition like PD where patients suffer from chronic motor impairments, it is paramount to assess the long-term symptom relief in an animal model of Parkinsonism.ObjectivesWe investigated whether 50-kHz USV playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen.MethodsIn phase 1, distance traveled and number of rearing behavior were assessed in an activity chamber in order to investigate whether sub-chronic haloperidol treatment induced psychomotor impairments. In phase 2, we investigated whether 50-kHz USV playback could overcome these impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50-kHz USV radial maze playback paradigm.ResultsSub-chronic haloperidol treatment led to psychomotor deficits since the distance traveled and number of rearing behavior were reduced as compared to saline control group or baseline. These psychomotor impairments were ameliorated during playback of 50-kHz USV, with haloperidol treated rats showing a clear social approach behavior towards the sound source exclusively during playback.ConclusionsThis study provides evidence that 50-kHz USV playback induces paradoxical kinesia in rats exhibiting motor deficits after sub-chronic haloperidol, as we previously showed after acute haloperidol treatment.
Highlights
Resulting from a pathophysiologic loss or degeneration of dopaminergic neurons in the substantia nigra pars compacta and the development of neuronal Lewy bodies, Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms
The present study addressed the question whether 50kHz ultrasonic vocalizations (USV) playback ameliorates psychomotor deficits induced by haloperidol in a sub-chronic dosing regimen implemented by drug administration via osmotic mini-pumps
In phase 2, we investigated whether 50-kHz USV playback could overcome these psychomotor impairments by assessing exploratory behaviors and approach behavior towards the sound source in the 50kHz USV radial maze playback paradigm
Summary
Resulting from a pathophysiologic loss or degeneration of dopaminergic neurons in the substantia nigra pars compacta and the development of neuronal Lewy bodies, Parkinson’s disease (PD) is characterized by both motor and non-motor symptoms. PD patients classically display rest tremor, rigidity, bradykinesia, and stooping posture. Drugs aimed at increasing DA activity are prescribed to PD patients. Antipsychotics belonging to the first generation of antipsychotic drugs (McCue et al 2006), such as haloperidol, block and reduce the effects of DA and even in therapeutic doses, can cause severe extrapyramidal side effects resembling PD symptoms (Lockwood and Remington 2015). These side effects may differ after acute and chronic exposure.
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