A new rodent model for neuroleptic-induced pseudo-Parkinsonism: Low doses of haloperidol increase forelimb tremor in the rat.

Abstract

Rats were trained to use the right forelimb to exert continuous downward pressure on a force transducer and simultaneously to drink sweetened milk from a dipper controlled by the emitted force. Oscillations in forelimb force during this performance were spectrally analyzed to describe the tremorogenic effects of haloperidol (0.04, 0.08, or 0.16 mg/kg). Haloperidol reduced time-on-task and increased the variance of force oscillations in the 10.0-25.0-Hz frequency band. When atropine sulfate (5 mg/kg) was given along with haloperidol, time-on-task was partially restored, and the effects of haloperidol on the 10.0-25.0-Hz band were diminished. These data suggest that the behavioral deficits produced by relatively low doses of haloperidol in rats are analogous (and possibly homologous) to neuroleptic-induced Parkinsonian symptoms in humans.

Subchronic effects of clozapine and haloperidol on rats' forelimb force and duration during a press-while-licking task

“…In contrast to clozapine, haloperidol did not affect the dominant frequency in the power spectrum. Although haloperidol's effects on forelimb force and on power density in the frequencies above 10 Hz were in the expected direction (i.e., elevation of the measures; Fowler et al 1990, the effects in the present study were not statistically significant. The lack of a significant effect was probably a result of doses generally falling below the 0.08 mg/kg which had the largest effect on forelimb force in the previous studies.…”

“…The operanda were 18 mm diameter disks that were rigidly attached to Model 31 load cells (0-250 g range, Sensotec, Columbus, Ohio, USA), which continuously measured the force exerted on the disk by the forelimb. The spatial arrangement of the aperture, the manipulandum, and the raised dipper cup was such that the trained rat could press the manipulandum with extended forepaw and drink from the dipper cup at the same time (for specific dimensions of apparatus, see Fowler et al 1990). …”

Similarities and differences between the subchronic and withdrawal effects of clozapine and olanzapine on forelimb force steadiness

“…The operandum was 18 mm diameter disk rigidly attached to a Model 31 load cell (0-250 g range; Sensotec, Columbus, Ohio, USA), which continuously measured the force exerted on the disk by the forelimb. The locations of the aperture, the manipulandum, and the raised dipper cup were such that the trained rat could press the manipulandum with a single extended forepaw and drink from the dipper cup at the same time (for specific dimensions of apparatus, see Fowler et al 1990). …”

Animal behavioral methods in neurotoxicity assessment: SGOMSEC joint report.

“…Further, operant techniques also permit the quantification of variables such as force and duration of selected limb movements and the detection and analysis of tremor (11,76,92,93). Such techniques demonstrate the high degree of selectivity that can be achieved using behavioral methods for measuring motor impairment.…”

“…Different behavioral paradigms for measuring sensory functions using conditioned and unconditioned behaviors, for example, have been successfully used to study visual (6), auditory (7) and somatosensory (8) changes produced by long-term neurotoxic exposures. Behavioral methods have also been developed for quantifying neurotoxicant effects on different aspects of specific motor functions including, for example, neuromuscular strength (9), whole-body and limb tremor (10,11), and alterations in gait (12). Further, cognitive behaviors such as the performance of learned tasks and processes related to attention, learning, and memory are also amenable to study using behavioral methodologies (13).…”