Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine.
BACKGROUND
Both harmaline and physostigmine are known to produce whole-body tremors in rodents, yet there is little quantitative information on the differential frequency characteristics of these tremors or on other possible motor effects of these drugs. In addition, the degree to which tolerance develops to their tremorogenic effects is uncertain.


OBJECTIVE
The purpose of this work was to use a new kind of instrument (the force-plate actometer) to describe quantitatively the frequency characteristics of tremor induced by the two drugs and simultaneously to measure locomotor activity effects. Another aim was to detect any tolerance effects on the tremor or locomotor measurements.


METHODS
Sprague-Dawley rats in four separate groups received harmaline (0, 4.0, 8.0, and 16.0 mg/kg) while another four groups received physostigmine (0, 0.10, 0.25, and 0.50 mg/kg). Dosing continued for 4 consecutive days. Each day, every rat's whole-body tremor and locomotor activity were recorded for 30 min. Fourier analysis of the force-plate recordings was used to quantify tremor and characterize its frequency components.


RESULTS
Harmaline induced a dose-related tremor that peaked in the 10 Hz region of the spectrum, while the dose related-tremor of physostigmine was demonstrably of a broader-band frequency composition. While harmaline tremor exhibited pronounced tolerance, physostigmine tremor remained substantial across the 4 days of dosing. Both drugs suppressed locomotor activity, and there was no tolerance on this measure for either drug.


CONCLUSIONS
In regard to tremor, harmaline and physostigmine induced quantitatively different kinds of tremor, and these differences probably reflect the drugs' different sites of action in the brain (harmaline: inferior olive; physostigmine: basal ganglia). For harmaline, tolerance to the tremorogenic effect was concurrent with a lack of tolerance to locomotor suppression, and this finding suggested the presence of a strong motor effect of harmaline that continued to be expressed despite the absence of tremor.
Wang
G
G
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA. fowler@falcon.ukans.edu
Fowler
S C
SC
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology; D006246:Harmaline / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014202:Tremor / Q000139:chemically induced* / Q000503:physiopathology
D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D006246:Harmaline