Effects of norcocaine and some norcocaine derivatives on schedule-controlled behavior of pigeons and squirrel monkeys
Spealman, R.D.; Goldberg, S.R.; Kelleher, R.T.; Morse, W.H.; Goldberg, D.M.; Hakansson, C.G.; Nieforth, K.A.; Lazer, E.S.
Journal of Pharmacology and Experimental Therapeutics 210(2): 196-205
1979
ISSN/ISBN: 0022-3565 PMID: 110921 Document Number: 147201
The growing abuse of cocaine has generated renewed interest in its behavioral effects and those of its derivatives. The behavioral effects of norcocaine, three N-alkylated derivatives of norcocaine (N-allyl-norcocaine, N-dimethylallyl-norcocaine, N-cyclopropylmethyl-norcocaine) and a phenyltropane analog of norcocaine (WIN 35,981) were compared with those of cocaine and a phenyltropane analog of cocaine (WIN 35,065-2). Squirrel monkeys and pigeons responded under a multiple fixed-interval, fixed-ratio schedule of food presentation; squirrel monkeys also responded under a multiple fixed-interval, fixed-ratio schedule of termination of a stimulus associated with electric shock. The effects of the drugs were quanitatively similar in each species, and depended mainly on the type of schedule (fixed-interval; fixed-ratio) that controlled responding. In the fixed-interval components, some doses of each drug increased responding; maximal increases in responding were similar with each drug. Each drug also altered the pattern of responding in the fixed-interval components; suitable doses increased the low rates of responding, which occurred early in the intervals, but decreased higher rates of responding, which occurred later in the intervals. In the fixed-ratio components, each drug decreased responding in a dose-related manner; decreases resulted both from increased periods of pausing and from decreased rates of responding once responding began. Neither N-allyl-norcocaine nor N-cyclopropylmethyl-norcocaine antagonized the rate-decreasing effects of cocaine under a fixed-ratio schedule of food presentation. Norcocaine and its N-alkylated derivatives had the most rapid onsets of effects and shortest durations of effect, followed in order by cocaine, WIN 35,981 and WIN 35,065-2. Norcocaine and its N-alkylated derivatives were about equipotent, WIN 35,065-2 was 3-10 times more potent than cocaine, and cocaine and WIN 35,065-2 were each 2-3 times more potent than their respective N-demethylated derivatives, norcocaine and WIN 35,981.