QUANTIFICATION OF THE HINDLIMB EXTENSOR THRUST RESPONSE IN RATS

This report describes a procedure for measuring the extensor thrust re sponse (ETR) and summarizes the results of initial validation experime nts using adult Long-Evans rats. The ETR can be quickly elicited and t he force measured by pressing against the hindlimb footpads with a sma ll rectangular plate or bar attached to a digital force gauge. Output of the force gauge is analyzed and displayed with commercially availab le hardware and software. The first experiment compared the acute effe cts of TP injection of chlorpromazine (CPZ; 1, 4, or 7 mg/kg) or amphe tamine (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 a nd FL/HL-GS values. Both 1 and 3 mg/kg AMP increased grip strength val ues but decreased ETR values. A second experiment compared the evoluti on of changes in ETR, FL/HL-GS, and peripheral neurophysiological meas ures during 8 weeks of daily oral dosing of 10 mg/kg acrylamide (ACR) monomer. ACR-treated rats exhibited a progressive decrease in ETR begi nning after 3 weeks of dosing, whereas a reduction of HL-GS was observ ed beginning much later, after 7 weeks of dosing. The deficit in ETR p rogressed in the absence of any changes in spontaneous or evoked elect rophysiological abnormalities in neuromuscular function, but was accom panied by a decrease in peripheral nerve conduction velocity. Taken to gether, 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 info rmation provided by FL/HL-GS, and suggest a hypothesis that the ETR ma y be sensitive to neurotoxicant-induced changes in somatosensory funct ion. (C) 1997 Elsevier Science Inc.