Acute Effects of Cocaine on Spontaneous and Discriminative Motor Functions: Relation to Route of Administration and Pharmacokinetics

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Journal of Pharmacology and Experimental Therapeuics

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Rats administered cocaine i.p. and p.o. (7.5-30 mg/kg) showed dose-related increases in locomotor (LM) and small-movement activities, with LM rates decreasing over the 2-hr session, except at the largest i.p. dose, for which rates were greater in the 2nd hr. Lidocaine p.o. (15-30 mg/kg) did not increase activity. Relating the area under the curve measures for serum cocaine (concentration-time) and LM activity (LM activity-time) for 2 hr postadministration indicated that cocaine was about twice as potent i.p., compared to p.o., in increasing LM activity. Cocaine (i.p. and p.o.) produced dose-related decrements in both discriminative motor control performance and in task work rate, whereas lidocaine p.o. did not. The motor control decrements produced by cocaine were approximately comparable by i.p. and p.o. routes, whereas effects on LM rates were much greater by i.p. than by p.o. administration. The effects of cocaine by both routes on LM rates were proportionally much greater than its effect on motor control performance. Changes in LM rates and motor control performance over the postadministration period were related to the pharmacokinetic features (maximum serum concentration, time to maximum serum concentration and elimination half-life) of cocaine observed for the routes explored (i.p., p.o. and s.c.). Tail-tip serum samples, although yielding conservative estimates of cocaine concentration, correlated well with trunk serum and brain cocaine levels.