Abstract
The discriminative stimulus effects of several local anesthetics and (+)-amphetamine were assessed in a drug discrimination based on the psychomotor stimulant cocaine. Two groups of adult male Sprague-Dawley rats were trained in two-lever operant chambers in a cocaine versus saline discrimination, or a cocaine versus procaine or saline discrimination, using a fixed ratio 20 schedule of food reinforcement. Cocaine, (+)-amphetamine and dimethocaine all dose-dependently substituted for the training dose of cocaine (10 mg/kg) in both procedures. While procaine and lidocaine showed partial substitution in the cocaine versus saline procedure, much less substitution occurred in the cocaine versus procaine or saline discrimination. These data demonstrate that it is possible to train rats to discriminate between cocaine and another local anesthetic procaine, resulting in an increased pharmacological specificity of cocaine discrimination. The fact that dimethocaine fully substituted for cocaine in both procedures indicates that this local anesthetic has more cocaine-like effects than others so far tested, which is consistent with results from other behavioral and neurochemical studies with this compound.
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References
Balster RL (1988) Pharmacological effects of cocaine relevant to its abuse. In: Clouet D, Ashgar K, Brown R (eds) Mechanisms of cocaine abuse and toxicity (NIDA Research Monograph 88, DHHS pub no. ADM 88-1585). US Govt Printing Office, Washington, DC, pp 1–13
Balster RL, Carroll FI, Graham JH, Mansbach RS, Rahman MA, Philip A, Lewin AH, Showalter VM (1991) Potent substituted-3β-phenyltropane analogs of cocaine have cocaine-like discriminative stimulus effects. Drug Alcohol Depend 29:145–151
Bergman J, Madras BK, Johnson SE, Spealman RD (1989) Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys. J Pharmacol Exp Ther 251:150–155
Callahan PM, Appel JB, Cunningham KA (1991) Dopamine D1 and D2 mediation of the discriminative stimulus properties ofd-amphetamine and cocaine. Psychopharmacology 103:50–55
Colpaert FC, Niemegeers CJE, Janssen PAJ (1978) Discriminative stimulus properties of cocaine andd-amphetamine, and antagonism by haloperidol: a comparative study. Neuropharmacology 17:937–942
de la Garza R, Johanson CE (1983) The discriminative stimulus properties of cocaine in rhesus monkey. Pharmacol Biochem Behav 19:145–148
Emmett-Oglesby MW, Spencer DG, Arnoult DE (1982) A TRS-80-based system for the control of behavioral experiments. Pharmacol Biochem Behav 17:583–587
Ford RD, Balster RL (1977) Reinforcing properties of intravenous procaine in rhesus monkeys. Pharmacol Biochem Behav 6:289–296
Hammerbeck DM, Mitchell CL (1978) The reinforcing properties of procaine andd-amphetamine compared in rhesus monkeys. J Pharmacol Exp Ther 204:558–569
Huang JT, Wilson MC (1982) Discriminative stimulus properties of cocaine and other local anesthetics in rats. Res Commun Subst Abuse 3:129–140
Huang JT, Wilson MC (1986) Comparative discriminative stimulus properties ofdl-cathinone,d-amphetamine, and cocaine in rats. Pharmacol Biochem Behav 24:205–210
Järbe TUC (1984) Discriminative stimulus properties of cocaine. Effects of apomorphine, haloperidol, procaine and other drugs. Neuropharmacology 23:899–907
Johanson CE (1980) The reinforcing properties of procaine, chloroprocaine, and proparacaine in rhesus monkeys. Psychopharmacology 67:189–194
McKenna ML, Ho BT (1980) The role of dopamine in the discriminative stimulus properties of cocaine. Neuropharmacology 19:298–303
Overton DA (1982) Multiple drug training as a method for increasing the specificity of the drug discrimination procedure. J Pharmacol Exp Ther 221:166–172
Overton DA, Shen CF, Ye GY, Gazdick LP (1989) Discriminable effects of phencyclidine analogs evaluated by multiple drug (PCP versus other) discrimination training. Psychopharmacology 97:514–520
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223
Silverman PB (1990) Cocaine and local anesthetics: stimulant activity in rats with nigral striatal lesions. Psychopharmacology 102:269–272
Silverman PB, Schultz KA (1989) Comparison of cocaine and procaine discriminative stimuli. Drug Dev Res 16:427–433
Spealman RD, Bergman J, Madras BK (1991) Self-administration of the high-affinity cocaine analog 2β-carbomethoxy-3β-(4-fluorphenyl) tropane. Pharmacol Biochem Behav 39:1011–1013
Woods JH, Winger GD, France CP (1987) Reinforcing and discriminative stimulus effects of cocaine: analysis of pharmacological mechanisms. In: Fisher S, Raskin A, Uhlenhuth EH (eds) Cocaine: clinical and biochemical aspects. Oxford University Press, New York, pp 21–65
Woolverton WL, Balster RL (1979) Reinforcing properties of some local anesthetics in rhesus monkeys. Pharmacol Biochem Behav 11:669–672
Woolverton WL, Balster RL (1982) Behavioral pharmacology of local anesthetics: reinforcing and discriminative stimulus effects. Pharmacol Biochem Behav 16:491–500
Zacny JP, Woolverton WL (1989) Discriminative stimulus properties of local anesthetics ind-amphetamine- and pentobarbital-trained pigeons. Pharmacol Biochem Behav 33:527–531
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Graham, J.H., Balster, R.L. Cocaine-like discriminative stimulus effects of procaine, dimethocaine and lidocaine in rats. Psychopharmacology 110, 287–294 (1993). https://doi.org/10.1007/BF02251283
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DOI: https://doi.org/10.1007/BF02251283