Abstract
The potency of cocaine, relative to d-amphetamine, to initiate and maintain intravenous self-administration behavior by dogs (n=5) was determined. Response-contingent infusions of cocaine (at unit doses of 0.15, 0.30 and 0.60 mg/kg/infusion) and d-amphetamine (at unit doses of 0.05 and 0.10 mg/kg/infusion) were available during daily 4-h sessions on a FR1 reinforcement schedule. By comparing the dose-response curves of the two drugs, it was found that 1 mg of amphetamine is equivalent to 5.3 mg of cocaine (95% confidence limits=3.8–9.1 mg). In a second experiment, pretreatment with the α-adrenergic antagonist phenoxybenzamine (in doses ranging from 0.125–2.0 mg/kg, IV) did not produce any appreciable changes in responding for cocaine (0.2 mg/kg/infusion) by dogs (n=9). In contrast, when the same animals were pretreated with the dopaminergic antagonist pimozide (in doses ranging from 5–40 mg/kg, IV), subsequent responding for cocaine was increased in a dose-dependent manner. In a third experiment it was determined that norcocaine, the N-demethylated metabolite of cocaine, would maintain self-administration behavior by dogs (n=4) when it was substituted for cocaine. As expected, when saline was substituted for cocaine, responding was not maintained.
Similar content being viewed by others
References
Andén N-E, Stromböm U (1974) Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia 38:91–103
Axelrod J (1954) Studies on sympathomimetic amines. II. The biotransformation and physiological disposition of d-amphetamine, d-p-hydroxyamphetamine and d-methamphetamine. J Pharmacol Exp Ther 110:315–326
Cicero TJ, Meyer ER, Smithloff BR (1974) Alpha adrenergic blocking agents: Antinociceptive activity and enhancement of morphine-induced analgesia. J Pharmacol Exp Ther 189:72–82
Cone EJ, Risner M, Neidert GL (1978) Concentrations of phenethylamine in dog following single doses and during intravenous self-administration. Res Commun Chem Pathol Pharmacol 22:211–232
Deneau GA, Yanagita T, Seevers M (1969) Self-administration of psychoactive substances by the monkey. Psychopharmacologia 16:30–48
DeWit H, Wise RA (1977) Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine or phenoxybenzamine. Can J Psychol 31:195–203
D'Mello GD, Stolerman IP (1977) Comparison of the discriminative stimulus properties of cocaine and amphetamine in rats. Br J Pharmacol 61:415–422
Downs AD, Eddy NB (1932) The effect of repeated doses of cocaine in the dog. J Pharmacol Exp Ther 46:195–198
Downs DA, Harrigan SE, Wiley JN, Robinson TE, Labay RJ (1979) Continuous stimulant self-administration in rhesus monkeys. Res Commun Psychol Psychiat Behav 4:39–49
Ellinwood E, Kilbey M (eds) (1977) Cocaine and other stimulants. Advances in behavioral biology, vol 21. Plenum, New York
Finney DJ (1971) Statistical method in biological assay. Griffin, London
Fischman MW, Schuster CR, Resnekov L, Schick J, Krasnegor N, Fennell W, Freedman D (1976) Cardiovascular and subjective effects of intravenous cocaine administration in humans. Arch Gen Psychiatry 33:983–989
Gill CA, Holz WC, Zirkle CL, Hill H (1978) Pharmacological modification of cocaine and apomorphine self-administration in the squirrel monkey. In: Deniker P, Radonco-Thomas C, Villeneuve A (eds) Neuro-psychopharmacology, Proceedings of the Tenth Congress of the Collegium Internationale Neuropsychopharmacologium. Pergamon Press, Oxford, pp 1477–1484
Hatch RC, Fischer R (1972) Cocaine-elicited behavior and toxicity in dogs pretreated with synaptic blocking agents, morphine, or diphenylhydantoin. Pharmacol Res Commun 4:383–392
Hawks RL, Kopin IJ, Colburn RW, Thoa NB (1974) Norcocaine: A pharmacologically active metabolite of cocaine found in the brain. Life Sci 15:2189–2195
Johanson CE, Kandel DA, Bonese K (1976) The effects of perphenazine on self-administration behavior. Pharmacol Biochem Behav 4:427–433
Jones BE (1977) Predicting abuse liability of depressant drugs. In: Thompson T, Unna K (eds) Predicting dependence liability of stimulant and depressant drugs. University Park Press, Baltimore, pp 35–46
Jones BE, Prada JA (1973) Relapse to morphine use in the dog. Psychopharmacologia 30:1–12
Masuoko D-L, Appelgren L, Hansson E (1967) Autoradiographic distribution studies of adrenergic blocking agents. I. 14C-phenoxybenzamine (Bensylyt NFN), α-adrenergic blocking agent. Acta Pharmacol Toxicol 25:113–122
McKenna ML, Ho BT, Englert LF (1979) Generalization of norcocaine to the discriminative stimulus properties of cocaine. Pharmacol Biochem Behav 10:273–276
Misra AL, Nayak PK, Bloch R, Mule SJ (1975) Estimation and disposition of 3H-benzoylecognine and pharmacological activity of some cocaine metabolites. J Pharm Pharmacol 27:784–785
Misra AL, Nayak PK, Patel MN, Vadlamani NL, Mule SJ (1974) Identification of norcocaine as a metabolite of [3H]-cocaine in rat brain. Experientia 30:1312–1314
Misra AL, Patel MN, Alluri R, Mule SJ, Nayak PK (1976) Disposition and metabolism of [3H] cocaine in acutely and chronically treated dogs. Xenobiotica 6:537–552
Pickens RW, Thompson T (1968) Cocaine-reinforced behavior in rats: Effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther 161:122–129
Risner ME, Jones BE (1975) Self-administration of CNS stimulants by dog. Psychopharmacologia (Berl.) 43: 207–313
Risner ME, Jones BE (1976a) Characteristics of unlimited access to self-administered stimulant infusions in dogs. Biol Psychiatry 11:625–634
Risner ME, Jones BE (1976b) Role of noradrenergic and dopaminergic processes in amphetamine self-administration. Pharmacol Biochem Behav 5:477–482
Risner ME, Jones BE (1977) Characteristics of β-phenethylamine self-administration by dog. Pharmacol Biochem Behav 6:689–696
Risner ME, Jones BE (1979) The effects of psychomotor stimulants on single-spatial alternation behavior in dogs. Psychopharmacology 63:137–141
Schuster CR, Johanson CE (1974) The use of animal models for the study of drug dependence. In: Gibbins RJ, Israel Y, Kalant H, Popham RE, Schmidt W, Smart RG (eds) Research advances in alcohol and drug problems. John Wiley and Sons, New York, pp 1–31
Thompson T, Unna K (eds) (1977) Predicting dependence liability of stimulant and depressant drugs. University Park Press, Baltimore
Vaupel DB, Martin WR (1976) Actions of methoxamine and tryptamine and their interactions with cyproheptadine and phenoxybenzamine on cat spinal cord segmental reflexes. J Pharmacol Exp Ther 196:87–96
Villarreal JE, Guzman M, Smith CB (1973) A comparison of the effects of d-amphetamine and morphine upon the locomotor activity of mice treated with drugs which alter brain catecholamine content. J Pharmacol Exp Ther 187:1–7
Wallach MB, Gershon S (1971) A neuropsychopharmacological comparison of d-amphetamine, l-Dopa and cocaine. Neuropharmacology 10:743–752
Weeks JR (1962) Experimental morphine addiction: Method for automatic intravenous injections in unrestrained rats. Science 138:143–144
Wilson MC, Schuster CR (1972) The effects of chlorpromazine on psychomotor stimulant self-administration in the rhesus monkey. Psychopharmacologia 26:115–126
Wilson MC, Schuster CR (1973) The effects of stimulants and depressants on cocaine self-administration behavior in the rhesus monkey. Psychopharmacologia 31:291–304
Wilson MC, Schuster CR (1974) Aminergic influences on intravenous cocaine self-administration by rhesus monkeys. Pharmacol Biochem Behav 2:563–571
Wilson MC, Hitomi M, Schuster CR (1971) Psychomotor-stimulant self-administration as a function of dosage per injection in the rhesus monkey. Psychopharmacologia 22:271–281
Wilson MC, Bedford JA, Kibbe AH, Sam JA (1978) Comparative pharmacology of norcocaine in M. mulatta and M. fascicularis. Pharmacol Biochem Behav 9:141–145
Woods JH (1977) Behavioral effects of cocaine in animals. In: Cocaine: 1977, NIDA Research Monograph Series no. 13. National Institute on Drug Abuse, Rockville, Md., pp 63–95
Woods JH, Herling S, Winger G (1978) Chlorpromazine- and haloperidol-induced changes in some behavioral effects of cocaine and amphetamine. In: Deniker P, Radonco-Thomas C, Villeneuve A (eds) Neuro-psychopharmacology, Proceedings of the Tenth Congress of the Collegium Internationale Neuropsychopharmacologium. Pergamon Press, Oxford, pp 1485–1502
Yokel RA, Pickens R (1974) Drug level of d-and l-amphetamine during intravenous self-administration. Psychopharmacologia 34:255–264
Yokel RA, Wise R (1976) Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48:311–318
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Risner, M.E., Jones, B.E. Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology 71, 83–89 (1980). https://doi.org/10.1007/BF00433258
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00433258