Abstract
Four rhesus monkeys were trained to smoke cocaine-base under a progressive ratio (PR) schedule, with ten smoking trials available each day. Unit dose was varied from 0.25 to 3 mg/kg, and lidocaine (2 mg/kg) was substituted for cocaine. Number of responses and break-point on the PR schedule increased with dose while the number of smoke deliveries increased only slightly. Maximum daily smoke deliveries ranged from six to nine across monkeys. When lidocaine (2 mg/kg) was substituted for cocaine-base, responding decreased to approximately half of that maintained by cocaine, and when cocaine was reinstated, higher response rates returned. Cardiovascular changes associated with cocaine smoking were monitored with an indwelling radio transmitter. There was an initial decrease in heart rate (30 s) followed by a rapid rise and decline by the end of the 15-min trials. Blood pressure increased rapidly after trial onset and returned to pretrial baseline by 15 min. Over the eight trials completed during a session, heart rate and blood pressure steadily increased over presession baselines during the first four trials, but there was then a decline suggesting acute tolerance development. Observations of the monkeys after each trial revealed dilated pupils and slightly agitated, hyperactive behavior. These findings indicated that smoked cocaine-base was rapidly established as a reinforcer for monkeys, and the physiological effects were similar to those reported in studies of human subjects.
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References
Ambre JJ, Belknap SM, Nelson J, Ruo TI, Shin SG, Atkinson AJ (1988) Acute tolerance to cocaine in humans. Clin Pharmacol Ther 44:1–8
Ando K, Yanagita T (1981) Cigarette smoking in rhesus monkeys. Psychopharmacology 17:117–127
Carroll ME (1982) Rapid acquisition of oral phencyclidine self-administration in food-deprived and food-satiated rhesus monkeys. Pharmacol Biochem Behav 17:341–346
Carroll ME, Santi PA, Rudell RL (1981) A microcomputer system for the control of behavioral experiments. Pharmacol Biochem Behav 14:415–417
Carroll ME, Stitzer ML, Strain E, Meisch RA (1990) Behavioral pharmacology of ethanol and other drugs: emerging issues. In: Galanter M (ed) Recent developments in alcoholism, vol 8. Plenum, New York, pp 5–46
Cook CE, Jeffcoat AR, Perez-Reyes M (1985) Cocaine. In: Barnett G, Chiang NC (eds) Pharmacokinetics and pharmacodynamics of psychoactive drugs. Biomedical Publications, Forest City, California, pp 48–61
Fischman MW (1984) The behavioral pharmacology of cocaine in humans. In: Grabowski J (ed) Cocaine pharmacology, effects and treatment of abuse. NIDA Res Monogr No 50 DHHS publication (ADM) 84:1326, US Government Printing Office, Washington, DC pp 72–91
Fischman MW (1988) Behavioral pharmacology of cocaine. J Clin Psychiatry (Suppl) 49:10
Fischman MW, Schuster CR, Resnekov L, Schick FE, Krasnegor NA, Fennell W, Freedman DX (1976) Cardiovascular and subjective effects of intravenous cocaine administration in humans. Arch Gen Psychiatry 33:938–989
Fischman MW, Schuster CR, Hatano Y (1983) A comparison of the subjective and cardiovascular effects of cocaine and lidocaine in humans. Pharmacol Biochem Behav 18:123–127
Griffiths RR, Bradford DL, Brady JV (1979) Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons. Psychopharmacology 65:125–136
Hatsukami DK, Keenan RM, Carroll ME, Colon E, Gieske D, Wilson B, Huber M (1990) A method for delivery of precise doses of cocaine base to humans for smoking. Pharmacol Biochem Behav 36:1–7
Henningfield JE, Meisch RA (1976) Drinking device for rhesus monkeys. Pharmacol Biochem Behav 4:609–610
Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989) Cocaine-induced cocaine craving. Psychopharmacology 97:59–64
Jarvik ME (1967) Tobacco smoking in monkeys. Ann NY Acad Sci 142:280–294
Johanson CE (1984) Assessment of the dependence potential of cocaine in animals In: Grabowski J, (ed) Cocaine: pharmacology, effects and treatment of abuse. NIDA Res Monogr No 50 DHHS Publication (ADM) 84–1326, US Government Printing Office, Washington, DC, pp 54–71
Meisch RA, Carroll ME (1987) Oral drug self-administration: drugs as reinforcers. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 143–160
Meisch RA, Henningfield JE (1977) Drinking of ethanol by rhesus monkeys: experimental strategies for establishing ethanol as a reinforcer. Adv Exp Med Biol 85:443–463
Paly D, Jatlow P, Van Dyke C, Jeri FR, Byck R (1982) Plasma cocaine concentrations during cocaine paste smoking. Life Sci 3:731–738
Perez-Reyes M, Guiseppi SD, Ondrusek G, Jeffcoat AR, Cook CE (1982) Free-base cocaine smoking. Clin Pharmacol Ther 32:459–465
Pickens R, Thompson T, Muchow DC (1973) Cannabis and phencyclidine self-administration by animals. In: Goldberg L, Hoffmeister F (eds) Psychological dependence definition assessment in animals and man: theoretical and clinical implications Bayer Symposium IV, Psychic Dependence. Springer, Berlin Heidelberg New York, pp 78–86
Pybus RJ, Goldfarb TL, Jarvik ME (1969) A device for measuring cigarette smoking in monkeys. J Exp Anal Behav 12:88–90
Resnick RB, Kestenbaum RS, Schwartz LK (1977) Acute systemic effects of cocaine in man: a controlled study by intranasal and intravenous routes. Science 195:696–699
Rogers WR (1985) Effects of cigarette nicotine content on smoking behavior of baboons. Addict Behav 10:225–233
Siegel RK, Jarvik ME (1980) DMT self-administration by monkeys in isolation. Bull Psychon Soc 16:117–120
Siegel RK, Johnson CA, Brewster JM, Jarvik ME (1976) Cocaine self-administration in monkeys by chewing and smoking. Pharmacol Biochem Behav 4:461–467
Stecher PG (1968) The Merck Index, 8 edn. Rahway, New Jersey
USPHS (1988) National Household Survey on Drug Abuse: 1988 population estimates
Woods JH, Winger GD, France CP (1987) Reinforcing and discriminative stimulus effects of cocaine. In: Fisher S, Raskin A, Uhlenhuth EH (eds) Analysis of pharmacological mechanisms. Cocaine: clinical and biobehavioral aspects. Oxford University Press, New York, pp 21–65
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Carroll, M.E., Krattiger, K.L., Gieske, D. et al. Cocaine-base smoking in rhesus monkeys: reinforcing and physiological effects. Psychopharmacology 102, 443–450 (1990). https://doi.org/10.1007/BF02247123
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DOI: https://doi.org/10.1007/BF02247123