Changes in Neuronal Activity in the Neostriatum and Reticular Formation Following Acute or Long-Term Amphetamine Administration

  • Philip M. Groves
  • George V. Rebec
Part of the Advances in Behavioral Biology book series (ABBI, volume 21)


There is now considerable evidence to suggest that the sequential patterns of hyperkinesia and behavioral stereotypes observed in a wide variety of species following an injection of amphetamines are due, in large measure, to a facilitation of catecholaminergic transmission in the central nervous system (e.g., as recently reviewed by Groves and Rebec, 1976). Additional recent work (e.g., Roberts, Zis, and Fibiger, 1975; Kelly, Seviour, and Iversen, 1975) further implicates the caudate-putamen, or neostriatum, and its dopaminergic input from the substantia nigra, pars compacta, and associated dopaminergic cell groups in the brainstem, in the expression of the psychomotor stimulant effects of amphetamine. The reticular formation of the brainstem is supplied, in part, by noradrenergic terminals and, as suggested by Bradley and associates (e.g., Bradley and Elkes, 1957; Bradley and Key, 1958), this area may contribute to the expression of amphetamine-induced electroencephalographic arousal. This view is consistent with the wide variety of evidence suggesting that the reticular formation of the brainstem mediates electroencephalographic and behavioral arousal (e.g., Moruzzi and Magoun, 1949; Lindsley, Bowden, and Magoun, 1949; Lindsley, Schriener, Knowles and Magoun, 1950; Segal and Mandell, 1970) and the elementary forms of plasticity that these phenomena exhibit (e.g., Sharpless and Hasper, 1956; Groves and Lynch, 1972; Groves, Wilson, and Miller, in press).


Neuronal Activity Firing Rate Reticular Formation Neuronal Firing Spontaneous Firing Rate 
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  1. Angrist, B. and Gershon, S.: Dopamine and psychotic states: Preliminary remarks. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes. Usdin, E., Ed., pp. 211–219. New York: Raven Press, 1974.Google Scholar
  2. Boakes, R.J., Bradley, P.B., and Candy, J.M.: A neuronal basis for the altering action of (4)-amphetamine, Br. J. Pharmacol.45, 391–403 (1972).Google Scholar
  3. Bradley, P.B. and Elkes, J.: The effects of some drugs on the electrical activity of the brain, Brain 80, 77–117 (1957).PubMedCrossRefGoogle Scholar
  4. Bradley, P.B. and Key, B.J.: The effect of drugs on arousal responses produced by electrical stimulation of the reticular formation of the brain, Electroenceph. clin. Neurophysiol.10, 97–110 (1958).Google Scholar
  5. Butcher, S.G. and Butcher, L.L.: Origin and modulation of acetylcholine activity in the neostriatum, Brain Res. 71, 167–171 (1974).PubMedCrossRefGoogle Scholar
  6. Connor, J.D.: Caudate nucleus neurones: Correlation of the effects of substantia nigra stimulation with iontophoretic dopamine, J. Physiol. 208, 691–703 (1970).Google Scholar
  7. Coyle, J.T. and Snyder, S.H.: Catecholamine uptake by synaptosomes in homogenates of rat brain: Stereospecificity in different areas, J. Pharmac. exp. Ther. 170, 221–231 (1969).Google Scholar
  8. Ellinwood E.H.: Behavioral and EEG changes in the amphetamine model of psychosis. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes. Usdin, E., Ed., pp. 281–297. New York: Raven Press, 1974.Google Scholar
  9. Ellinwood, E.H., Sudilovsky, A., and Nelson, L.M.: Evolving behavior in the clinical and experimental amphetamine (model) psychosis, Am. J. Psychiat. 130, 1088–1093 (1973).Google Scholar
  10. Groves, P.M. and Lynch, G.S.: Mechanisms of habituation in the brainstem, Psychol. Rev. 79, 237–244 (1972).Google Scholar
  11. Groves, P.M., Miller, S.W., Parker, M.V., and Rebec, G.V.: Organization by sensory modality in the reticular formation of the rat, Brain Res. 64, 167–187 (1973).PubMedCrossRefGoogle Scholar
  12. Groves, P.M. and Rebec, G.V.: Biochemistry and behavior: Some central actions of amphetamine and antipsychotic drugs, A. Rev. Psychol. 27, 91–127 (1976).Google Scholar
  13. Groves, P.M., Rebec, G.V., and Harvey, J.A.: Alteration of the effects of (+)-amphetamine on neuronal activity in the striatum following lesions of the nigrostriatal bundle, Neuropharmacol. 14, 369–376 (1974).Google Scholar
  14. Groves, P.M., Rebec, G.V., and Segal, D.S.: The action of d-amphetamine on spontaneous activity in the caudate nucleus and reticular formation of the rat, Behay. Biol. 11, 33–47 (1974).Google Scholar
  15. Groves, P.M., Wilson, C.J., and Miller, S.W.: Habituation of the acoustic startle response: A neural systems analysis of habituation in the intact animal. In: Advances in Psychobiology.Google Scholar
  16. Riesen, A. and Thompson, R.F., Eds., Vol. 3. New York: Wiley, in press.Google Scholar
  17. Groves, P.M., Wilson, C.J., Young, S.J., and Rebec, G.V.: Self-inhibition by dopaminergic neurons, Science 190, 522–529 (1975).PubMedCrossRefGoogle Scholar
  18. Iversen, S.D. and Creese, I.: Behavioral correlates of dopaminergic supersensitivity, Adv. Neurol. 9, 81–92 (1975).Google Scholar
  19. Kalant, H., LeBlanc, A.E., and Gibbins, R.J.: Tolerance to and dependence on some non-opiate psychotropic drugs, Pharmac. Rev.23, 135–191 (1971).Google Scholar
  20. Kelly, P.H., Seviour, P.W., and Iversen, S.D.: Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum, Brain Res. 94, 507–522 (1975).PubMedCrossRefGoogle Scholar
  21. Klawans, H.L., Crossett, P., and Dana, N.: Effect of chronic amphetamine exposure on stereotyped behavior: Implications for pathogenesis of L-dopa induced dyskinesias, Adv. Neurol. 9, 105–112 (1975).Google Scholar
  22. Koenig, J.F.R. and Klippel, R.A. The Rat Brain: A Stereotaxic Atlas of the Forebrain and Lower Parts of the Brain Stem. Baltimore: Williams and Wilkins, 1963.Google Scholar
  23. Lewander, T.: Effect of chronic treatment with central stimulants on brain monoamines and some behavioral and physiological functions in rats, guinea pigs, and rabbits. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes.Google Scholar
  24. Usdin, E., Ed., pp. 221–240. New York: Raven Press, 1974.Google Scholar
  25. Lewander, T.: A mechanism for the development of tolerance to amphetamine in rats, Psychopharmacologia 13, 17–31 (1971).CrossRefGoogle Scholar
  26. Lindsley, D.B., Bowden, J., Magoun, H.W.: Effect upon EEG of acute injury to the brain stem activating system, Electroenceph. clin. Neurophysiol. 1, 475–486 (1949).Google Scholar
  27. Lindsley, D.B., Schriener, L.H., Knowles, W.B., Magoun, H.W.: Behavioral and EEG changes following chronic brain stem lesions in the cat, Electroenceph. clin. Neurophysiol. 2, 483–498 (1950).Google Scholar
  28. Lynch, G.S., Lucas, P.A., Deadwyler, S.A.: The demonstration of acetylcholinesterase containing neurons within the caudate nucleus of the rat, Brain Res. 45, 617–621 (1972).PubMedCrossRefGoogle Scholar
  29. Mcgeer, E.G., Mcgeer, P.L., Grewaal, D.S., and Singh, V.K.: Striatal cholinergic interneurons and their relation to dopaminergic nerve endings, J. Pharmacol. 6, 143–152 (1975).Google Scholar
  30. Mirsky, A.F.: Neuropsychological bases of schizophrenia, A. Rev. Psychol. 20, 321–348 (1969).Google Scholar
  31. Moruzzi, G. and Magoun, H.W.: Brain stem reticular formation and activation of the EEG, Electroenceph. clin. Neurophysiol. 1, 455–473 (1949).Google Scholar
  32. Racagni, G., Cheney, D.L., Trabucchi, M., and Costa, E.: In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum, J. Pharmac. exp. Ther. in press.Google Scholar
  33. Rebec, G.V. and Groves, P.M.: Differential effects of the optical isomers of amphetamine on neuronal activity in the reticular formation and caudate nucleus of the rat, Brain Res. 83, 301318 (1975a).Google Scholar
  34. Rebec, G.V. and Groves, P.M.: Apparent feedback from the caudate nucleus to the substantia nigra following amphetamine administration, Neuropharnacol. 14, 275–282 (1975b).CrossRefGoogle Scholar
  35. Rebec, G.V.: Neurophysiological correlates of long-term amphetamine treatment in rats. Unpublished Ph.D. dissertation, University of Colorado, 1975.Google Scholar
  36. Roberts, D.C.S., Zis, A.P., and Fibiger, H.C.: Ascending catecholamine pathways and amphetamine-induced locomotor activity: Importance of dopamine and apparent non-involvement of norepinephrine, Brain Res. 93, 441–454 (1975).PubMedCrossRefGoogle Scholar
  37. Segal, D.S.: Behavioral characterization of d-and 1-amphetamine: Neurochemical implications, Science 190, 475–477 (1975).PubMedCrossRefGoogle Scholar
  38. Segal, D.S. and Mandell, A.J.: Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy, Pharmacol. Biochem. Behay. 2, 249–255 (1974).Google Scholar
  39. Sharpless, S.: Reorganization of function in the nervous system-use and disuse, A. Rev. Physiol. 26, 357–388 (1964).Google Scholar
  40. Sharpless, S.: Supersensitivity-like phenomena in the central nervous system, Fed. Proc. 34, 1990–1997 (1975).Google Scholar
  41. Sharpless, S. and Jasper, H.H.: Habituation of the arousal reaction, Brain 79, 6550–680 (1956).CrossRefGoogle Scholar
  42. Snyder, S.H., Banerjee, S.P., Yamamura, H.I., and Greenberg, D.: Drugs, neurotransmitters and schizophrenia, Science 184, 12431253 (1974).Google Scholar
  43. Taylor, K.M. and Snyder, S.H.: Amphetamine: Differentiation by Band 1-isomers of behavior involving brain norepinephrine or dopamine, Science 168, 1487–1489 (1970).PubMedCrossRefGoogle Scholar
  44. Trabucchi, M., Cheney, D.L., Racagni, G., and Costa, E.: In vivo inhibition of striatal acetylcholine turnover by L-DOPA, apomorphine and (+)-amphetamine, Brain Res. 85, 130–134 (1975).PubMedCrossRefGoogle Scholar
  45. Ungerstedt, U., Ljundberg, T., Hoffer, B., and Siggins, G.: Dopaminergic supersensitivity in the neostriatum, Adv. Neurol. 9, 57–66 (1975).Google Scholar
  46. Wallach, M.B.: Drug-induced stereotyped behavior: Similarities and differences. In: Neuropsychopharmacology of Monoamines and Their Regulatory Enzymes. Usdin, E., Ed., pp. 241–260. New York: Raven Press, 1974.Google Scholar
  47. York, D.H.: The inhibitory action of dopamine on neurones of the caudate nucleus, Brain Res. 5, 263–266 (1967).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Philip M. Groves
    • 1
  • George V. Rebec
    • 2
  1. 1.University of ColoradoBoulderUSA
  2. 2.School of MedicineUniversity of California, San DiegoLa JollaUSA

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