Comparative behavioral profile of cocaine and norcocaine in rats and monkeys

Contribution of the active metabolite, norcocaine, to cocaine's effects after intravenous and oral administration in rats: pharmacodynamics

“…Norcocaine is a more potent local anesthetic than cocaine (Just and Hoyer 1977) and is more effective than cocaine in inhibiting norepinephrine uptake by brain synaptosomes (Hawks et al 1974). Behaviorally, cocaine, but not norcocaine, increases locomotor activity and fixed interval responding while both agents decrease fixed ratio (FR) responding (Spealman et al 1979;Bedford et al 1980;Elliott et al 1987).…”

“…Further verification of norcocaine's contribution to oral cocaine's effects on DRL performance required a behavioral paradigm in which norcocaine produced negligible effects. If norcocaine as a parent compound did not stimulate locomotor activity (Bedford et al 1980;Elliott et al 1987), then the formation of norcocaine after oral cocaine administration should have no contribution to oral cocaine's stimulatory effects. For this purpose, spontaneous activity was also evaluated using a separate, parallel group of animals to dissociate norcocaine's effects from those of cocaine.…”

Disposition of Cocaine in Pregnant Sheep: I. Pharmacokinetics

“…However, in in vitro prepa rations, these metabolites exhibited approxi mately 10% of the activity of cocaine in inhibiting monoamine uptake [14], Current interest in these compounds relates mainly to their forensic significance in confirming recent cocaine use [15], Minor metabolites of cocaine include norcocaine and other demethylated products. The formation of nor cocaine, estimated to be 2-6 % of cocaine in man [12], may be equipotent with cocaine in the ability to inhibit uptake of ^-norepi nephrine by synaptosomes prepared from rat brain [14], Direct administration of norco caine to monkeys produced behavioral ef fects suggesting it is a pharmacologically ac tive metabolite of cocaine [16]. We did not find norcocaine present in ewe or fetus after maternal cocaine administration.…”

“…The schedule included samples at the follow ing times after drug administration. 4,8,12,16,20,30,40,50,60,90, 120 and 240 min. A few animals had samples collected at 5, 10 and 15 min.…”

Subchronic nandrolone administration reduces cocaine-induced dopamine and 5-hydroxytryptamine outflow in the rat nucleus accumbens

“…In this study, cocaine produced a rapid and long-lasting increase in LMA and stereotypic behavior, as was to be expected since cocaine has been shown to produce LMA in rats (Bedford et al 1980), and with high doses, stereotyped behavior (Wellman et al 2002). Correlation analysis between neurochemical and behavioral data was carried out, and as seen from results, DA, its metabolites, and 5-HT concentrations correlates strongly with LMA and stereotyped behavior seen after stimulant dosing.…”