Abstract
Several doses (8–64 mg/kg) of β-phenylethylamine (PEA), a naturally-occurring sympathomimetic amine structurally related to amphetamine and with similar effects on animal behavior, were administered (IP, daily for ten days) to Fisher 344 rats that were trained to perform a shuttlebox conditioned avoidance response (CAR) at a high, stable rate. PEA 8 mg/kg did not influence avoidance responding after single or multiple injections. Acute administration of PEA 16 mg/kg produced dose-dependent disruptions of the CAR. With repeated administration, complete tolerance to CAR disruption was acquired by the third injection of PEA 16 mg/kg or by the fifth injection of PEA 32 mg/kg and maintained with both doses through ten injections; the use of appropriate controls indicated that tolerance was pharmacological and not behavioral. Over the course of ten injections, tolerance did not develop to shuttlebox disruption caused by 64 mg/kg, and this dose of PEA did not elicit tolerance to stereotyped behavior after 21 injections. These data were interpreted as showing differential tolerance to low vs. high dose effects of PEA: Lower doses produce tolerance to disruption of the CAR, but the highest dose did not because of the presence of incompatible response tendencies (e.g., stereotypy) interfering with the CAR. Our data showing development of tolerance to lower doses of PEA is the first demonstration in the literature that tolerance can develop to a behavioral effect of this compound.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Antelman, S. M., Edwards, D. J., Lin, M.: Phenylethylamine: Evidence for a direct, postsynaptic dopamine-receptor stimulating action. Brain Res. 127, 317–322 (1977)
Borison, R. L., Havdala, H. S., Diamond, B. I.: Chronic phenyethylamine stereotypy in rats: A new animal model for schizophrenia: Life Sci. 21, 117–122 (1977)
Cohen, I., Fischer, J. F., Vogel, W. H.: Physiological disposition of β-phenylethylamine, 2,4,5-trimethoxyphenylethylamine and β-hydroxymescaline in rat brain, liver and plasma. Psychopharmacologia 36, 77–84 (1974)
Gupta, B. D., Holland, H. C.: An examination of the effects of stimulant and depressant drugs on escape/avoidance conditioning in strains of rats selectively bred for emotionality/nonemotionality. Psychopharmacologia 14, 95–105 (1969)
Heller, B., Lumbreras, N.: Studies on the role of phenylethylamine in methylamphetamine action mecahnisms. Experientia 32, 210–211 (1976)
Howard, J. L., Pollard, G. T., Rohrbach, K. W., Harto, N. E.: Effect of β-phenylethylamine and d-amphetamine on electrical self-stimulation of brain. Pharmacol. Biochem. Behav. 5, 661–664 (1976)
Inwang, E. E., Mosnaim, A. D., Sabelli, H. C.: Isolation and characterization of phenylethylamine and phenylethanolamine from human brain. J. Neurochem. 20, 1469–1473 (1973)
Krieckhaus, E. E., Miller, N. E., Zimmerman, P.: Reduction of freezing behavior and improvement of shock avoidance by d-amphetamine. J. Comp. Physiol. Psychol. 60, 36–40 (1965)
Mogilnicka, E., Braestrup, C.: Noradrenergic influence on the stereotyped behavior induced by amphetamine, phenethylamine and apomorphine. J. Pharm. Pharmacol. 28, 253–255 (1976)
Moja, E. A., Stoff, D. M., Gillin, J. C., Wyatt, R. J.: β-phenylethylamine and animal behavior. In: Noncatecholic phenylethylamines. Part I. Phenylethylamine: Biological mechanisms and clinical aspects, A. D. Mosnaim, M. E. Wolf, eds., pp. 315–344. New York: Marcel Dekker 1978
Moja, E. A., Stoff, D. M., Gillin, J. C., Wyatt, R. J.: Dose-response effects of β-phenylethylamine on stereotyped behavior in pargylinepretreated rats. Biol. Psychiat. 11, 731–742 (1976)
Nakajima, T., Kakimoto, Y., Sano, I.: Formation of β-phenylethylamine in mammalian tissue and its effect on motor activity in the mouse. J. Pharmacol. Exp. Ther. 143, 319–325 (1964)
Saavedra, Enzymatic isotopic assay for and presence of β-phenylethylamine in brain. J. Neurochem. 22, 211–216 (1974)
Sabelli, H. C., Mosnaim, A. D.: Phenylethylamine hypothesis of affective behavior. Am. J. Psychiat. 131, 695–699 (1974)
Sandler, M., Reynolds, G. P.: Does phenylethylamine cause schizophrenia? Lancet 1976 I 70-71
Snyder, S. H.: Amphetamine psychosis: A model for schizophrenia mediated by catecholamines. Am. J. Psychiat. 130, 61–67 (1973)
Stoff, D. M., Moja, E. A., Gillin, J. C., Wyatt, R. J.: Dose-response and time course effects of N,N-dimethyltryptamine (DMT) on disruption of rat shuttlebox avoidance. Biol. Psychiat. 12, 339–346 (1977)
Tinklenberg, J. R., Gillin, J. C., Murphy, G., Staub, R., Wyatt, R. J.: The effects of phenylethylamine (PEA) in rhesus monkeys. Am. J. Psychiat. 135, 576–578 (1978)
Vasko, M. R., Lutz, M. P., Domino, E. F.: Structure activity relations of some indolealkylamines in comparison to phenethylamine on motor activity and acquisition of avoidance behavior. Psychopharmacologia 36, 49–58 (1974)
Winer, B. J.. Statistical Principles in Experimental Design, 2nd Edition. New York: McGraw Hill 1971
Wyatt, R. J., Gillin, J. C., Stoff, D. M., Moja, E. A., Tinklenberg, J. R.: β-phenylethylamine and the neuropsychiatric disturbances. In: Neuroregulators and psychiatric disorders, E. Usdin, J. Barchas, D. Hamburg, eds., pp. 31–45. New York: Oxford University Press 1977
Wyatt, R. J., Murphy, D. L.: Low platelet monoamine oxidase activity and schizophrenia. Schizophrenia Bull. 2, 77–89 (1976)
Yang, H.-Y. T., Neff, N. H.: β-phenylethylamine: A specific substrate for Type B monoamine oxidase of brain. J. Pharmacol. Exp. Ther. 187, 365–371 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stoff, D.M., Moja, E.A., Jeffery, D.R. et al. Tolerance development to a disruptive effect of β-phenylethylamine (PEA) on a learned behavior in rats. Psychopharmacology 66, 127–131 (1979). https://doi.org/10.1007/BF00427619
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427619