Abstract
The drug self-administration paradigm is routinely used to assess the abuse liability of psychoactive compounds. Investigations of the behavioral effects of drug use, however, often involve the response-independent (experimenter-delivered) administration of the compound. It is frequently assumed that response-independent presentation of a compound has the same effects as response dependent deliveries. The present study examined directly the effects of response-dependent (self-administered) versus response-independent (experimenter- delivered) administration of cocaine on food intake and lethality. Littermate triads were exposed to either cocaine (0.33 mg/infusion) or saline using a yoked-box procedure. One member of the triad self-administered the drug under a fixed-ratio 2 schedule. The other two rats received response-independent infusions of either cocaine or saline. Groups of triads were exposed to two different cocaine access conditions. Daily sessions were terminated after 6 h for one group and after the delivery of 80 infusions for the other. The mean number of infusions delivered each session was 47 (±12) and 70 (±11), respectively, for the 6-h and 80-infusion condition. Under the 80-infusion condition, response-independent infusions of cocaine resulted in a significantly higher rate of mortality compared to littermates self-administering identical amounts of the drug. A fewer number of deaths occurred under 6-h condition; however, only rats exposed to response-independent infusions died under both access conditions. These data indicate that the presence or absence of response dependency can profoundly alter the lethal effects of cocaine.
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Ator NA, Griffiths RR (1992) Differential sensitivity to madozlam discriminative-stimulus effects following self-administered versus response-independent midazolam. Psychopharmacology 110:1–4
Barrett JE (1987) Nonpharmacological factors determining the behavioral effects of drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of Progress. Raven Press, New York, pp 1493–1501
Brady JV, Porter RW, Conrad DG, Mason JW (1958) Avoidance behavior and the development of gastroduodenal ulcers. J Exp Anal Behav 1:69–72
Dworkin SI, Mirkis S, Smith JE (1990) Reinforcer interactions under concurrent schedules of food, water and intravenous cocaine, Behav Pharmacol 1:327–338
Ettenberg A, Geist TD (1991) Animal model for investigating the anxiogenic effects of self-administered cocaine. Psychopharmacology 103:455–61
Goldberg SR, Spealman RD (1982) Maintenance and suppression of behavior by intravenous nicotine injections in squirrel monkeys, Fed Proc 1:216–20
Goldberg SR, Spealman RD (1983) Suppression of behavior by intravenous injections of nicotine or by electric shocks in squirrel monkeys. Effects of chlordiazepoxide and mecamylamine. J Pharmacol Exp Ther 224:334–340
Goldberg SR, Spealman RD, Goldberg DM (1981) Persistent behavior at high rates maintained by intravenous self-administration of nicotine. Science 214:573–575
Johanson CE, Schuster CR (1981) Animal models of drug self-administration. In: Mello NK (ed) Advances in substance abuse: behavioral and biological research. Jai Press, Greenwich, Connecticut, Vol 2, pp 217–297
Kelleher RT, Morse WH (1968) Schedules using noxious stimuli, III: Responding maintained with response-produced electric shock. J Exp Anal Behav 11:819–838
McKearney JW (1968) Maintenance of responding under a fixed-interval schedule of electric shock-presentation. Science 160:1249–1251
McKearney JW (1972) Maintenance and suppression of responding under schedules of electric shock presentation. J Exp Anal Behav 17:425–432
Mello NK, Mendelson JH (1970) Experimentally induced intoxication in alcoholics: a comparison between programmed and spontaneous drinking. J Pharmacol Exp Ther 173:271–298
Morse WH, Kelleher RT (1977) Determinants of reinforcement and punishment. In: Honig WK, Staddon JER (eds) Handbook of operant behavior. Prentice-Hall, Englewood Cliffs, New Jersey, pp 174–200
Siegel S (1988) Drug anticipation and drug tolerance. In: Lader M (ed) The psychopharmacology of addiction. Oxford University Press, New York, pp 73–96
Spealman RD 1979) Behavior maintained by the termination of a schedule of self-administered cocaine. Science 204:1231–1233
Spealman RD 1983) Maintenance of behavior by postponement of scheduled injections of nicotine in squirrel monkeys. J Pharmacol Exp Ther 27:154–159
Spealman RD, Goldberg SR (1982) Maintenance of schedule-controlled behavior by intravenous injections of nicotine in squirrel monkeys. J Pharmacol Exp Ther 223:402–408
Steiner SS, Beer B, Shaffer MM (1969) Escape from self-produced rates of brain stimulation. Science 163:90–91
Weiss JM (1970) Somatic effects of predictable and unpredictable shock. Psychosom Med 32:397–408
Weiss JM (1972) Psychological factors in stress and disease. Sci Am 226:104–113
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Dworkin, S.I., Mirkis, S. & Smith, J.E. Response-dependent versus response-independent presentation of cocaine: differences in the lethal effects of the drug. Psychopharmacology 117, 262–266 (1995). https://doi.org/10.1007/BF02246100
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DOI: https://doi.org/10.1007/BF02246100