Quantification of the hindlimb extensor thrust response in rats.
This report describes a procedure for measuring the extensor thrust response (ETR) and summarizes the results of initial validation experiments using adult Long-Evans rats. The ETR can be quickly elicited and the force measured by pressing against the hindlimb footpads with a small rectangular plate or bar attached to a digital force gauge. Output of the force gauge is analyzed and displayed with commercially available hardware and software. The first experiment compared the acute effects of i.p. injection of chlorpromazine (CPZ; 1, 4, or 7 mg/kg) or amphetamine (AMP; 0.3, 1, or 3 mg/kg) on the ETR and forelimb/hindlimb grip strength (FL/HL-GS) in male and female rats. CPZ decreased both ETR and FL/HL-GS values. Both 1 and 3 mg/kg AMP increased grip strength values but decreased ETR values. A second experiment compared the evolution of changes in ETR, FL/HL-GS, and peripheral neurophysiological measures during 8 weeks of daily oral dosing of 10 mg/kg acrylamide (ACR) monomer. ACR-treated rats exhibited a progressive decrease in ETR beginning after 3 weeks of dosing, whereas a reduction of HL-GS was observed beginning much later, after 7 weeks of dosing. The deficit in ETR progressed in the absence of any changes in spontaneous or evoked electrophysiological abnormalities in neuromuscular function, but was accompanied by a decrease in peripheral nerve conduction velocity. Taken together, the results indicate that the ETR can be used to characterize functional effects in both single dose and repeated dose experiments. The data also indicate that the ETR does not merely duplicate the information provided by FL/HL-GS, and suggest a hypothesis that the ETR may be sensitive to neurotoxicant-induced changes in somatosensory function.
Ross
J F
JF
Human and Environmental Safety Division, Miami Valley Laboratories, Procter & Gamble Company, Cincinnati, OH 45239-8707, USA.
Handley
D E
DE
Fix
A S
AS
Lawhorn
G T
GT
Carr
G J
GJ
D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology* / Q000633:toxicity; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003864:Depression, Chemical; D003913:Dextroamphetamine / Q000494:pharmacology; D005260:Female; D005552:Forelimb / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D002491:Central Nervous System Agents; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine; D002746:Chlorpromazine