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An improved foot-shock titration procedure in rats for centrally acting analgesics.

A foot-shock titration method for the measurement of antinociceptive activity in the rat has been developed. A new grid design is described which makes the use of scrambled shocks unnecessary. Thresholds for responses elicited at different levels of integration within the central nervous system are measured: Detection threshold, flexor reflex, coordinated jumping and vocalization. These thresholds were found to be stable over time in saline-treated rats. The two opioid analgesics morphine and d-propoxyphene increased these thresholds, each in a characteristic way. Morphine was more selective in its action and significantly more effective in increasing the vocalization threshold than the threshold for jumping, whereas d-propoxyphene increased both these thresholds to the same extent. Neither drug affected the detection threshold in low to moderate doses. The difference in pharmacodynamic profile is discussed in terms of heterogeneity of opioid receptor-effector mechanisms at different levels of the neuroaxis.