Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Quantitative assessment of the microstructure of rat behavior: II. Distinctive effects of dopamine releasers and uptake inhibitors

  • 44 Accesses

  • 32 Citations


The effects of four indirect dopamine agonists,d-amphetamine (0.25–4.0 mg/kg), cocaine (2.5–40.0 mg/kg), GBR 12909 (10.0–30.0 mg/kg), and nomifensine (5.0–20.0 mg/kg), on the behavioral organization of movements in an unconditioned motor paradigm were investigated in rats. The extended scaling hypothesis using the fluctuation spectrum of local spatial scaling exponents was used to quantify the geometrical characteristics of movements. The results reveal a qualitatively similar disruption of behavioral organization by lower doses of these drugs. Specifically, rats treated withd-amphetamine (<2.0 mg/kg), cocaine (<20.0 mg/kg), GBR 12909 (<20.0 mg/kg), or nomifensine (<10.0 mg/kg) exhibited a reduced range in the fluctuation spectrum, reflecting a predominance of meandering movements with local spatial scaling exponents between 1.3 and 1.7. This reduction was accompanied dynamically by a reduced predictability of movement sequences as measured by the dynamical entropy,h. By contrast, higher doses of these drugs produced distinctly different changes in behavioral organization. In particular, 4.0 mg/kgd-amphetamine and 40.0 mg/kg cocaine increased the fluctuation range, reflecting relative increases in both straight and circumscribed movements that are interpreted as a combination of spatially extended and local perseveration. In contrast, high doses of 30.0 mg/kg GBR 12909 and 20.0 mg/kg nomifensine induced only local perseveration. High doses ofd-amphetamine, cocaine, GBR 12909 and nomifensine reduced the dynamical entropy,h, indicating an increased predictability of the movement sequences. These results suggest that the generic behavioral change induced by low doses of dopamine agonists is characterized by a reduced variety of path patterns coupled with an increased variability in sequential movement sequences. The differential effects of higher doses of these drugs may be due to their influences on other neurotransmitter systems or differential affinities for different dopamine subsystems.

This is a preview of subscription content, log in to check access.


  1. Andersen PH (1989) The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action. Eur J Pharmacol 166:493–504

  2. Balster RL, Schuster CR (1973) A comparison ofd-amphetamine,l-amphetamine, and methamphetamine self-administration in rhesus monkeys. Pharmacol Biochem Behav 1:67–71

  3. Berger P, Elsworth JD, Arroyo J, Roth RH (1990) Interaction of [3H]GBR 12935 and GBR 12909 with the dopamine uptake complex in nucleus accumbens. Eur J Pharmacol 177:91–94

  4. Berlyne DE (1960) Conflict, arousal, and curiosity. McGraw Hill, New York

  5. Callaway CW, Wing L, Geyer MA (1990) Serotonin release contributes to the stimulant effects of 3,4-methylenedioxymethamphetamine in rats. J Pharmacol Exp Ther 254:456–464

  6. Carboni E, Imperato A, Perezzani L, Di Chiara G (1989) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience 28:653–661

  7. Creese I, Iversen SD (1974) The role of forebrain dopamine systems in amphetamine-induced stereotyped behavior in the rat. Psychopharmacology 39:345–357

  8. De La Garza R, Johanson CE (1983) The discriminative stimulus properties of cocaine andd-amphetamine: the effects of three routes of administration. Pharmacol Biochem Behav 24:765–768

  9. Dixon WJ (1989) BMDP Biomedical computer programs. University of California Press, Los Angeles

  10. Fibiger HC, Philips AG (1986) Reward, motivation, cognition: Psychobiology of mesotelencephalic dopamine systems. In Bloom FE (ed) Handbook of physiology, Vol 4 pp 647–675 American Physiological Society, Bethesda MD

  11. Flicker C, Geyer MA (1982) Behavior during hippocampal microinfusions: I. Norepinephrine and diversive exploration. Brain Res Rev 4:79–103

  12. Geyer MA (1982) Variational and probabilistic aspects of exploratory behavior in space: Four stimulant styles. Psychopharmacol Bull 18:48–51

  13. Geyer MA, Russo PV, Masten VL (1986) Multivariate assessment of locomotor behavior: Pharmacological and behavioral analyses. Pharmacol Biochem Behav 25:277–288

  14. Geyer MA, Russo PV, Segal DS, Kuczenski R (1987) Effects of apomorphine and amphetamine on patterns of locomotor and investigatory behavior in rats. Pharmacol Biochem Behav 28:393–399

  15. Goudie A, Reid D (1988) Qualitative discrimination between cocaine and amphetamine in rats. Eur J Pharmacol 151:471–474

  16. Gray T, Wise R (1980) Effect of pimozide on lever pressing behavior maintained on an intermittent reinforcement schedule. Pharmacol Biochem Behav 12:931–935

  17. Hill RT (1970) Facilitation of conditioned reinforcement as a mechanism of psychomotor stimulation. In: Costa E, Garattini S (eds) Amphetamine and related compounds. Raven, New York, p 781–795

  18. Huang D, Wilson MC (1986) Comparative discriminative stimulus properties ofdl-cathinone,d-amphetamine, and cocaine in rats. Pharmacol Biochem Behav 24:205–210

  19. Hurd YL, Ungerstedt U (1989) Cocaine: an in vivo microdialysis evaluation of its acute action on dopamine transmission in rat striatum. Synapse 3:48–54

  20. Iversen SD (1977) Neural substrates mediating amphetamine responses. In: Ellinwood EH Jr, Kilbey MM (eds) Cocaine and other stimulants. Plenum, New York, pp 31–45

  21. Jarbe TUC (1981) Cocaine cue in pigeons: time course studies and generalization to structurally related compound (Norcocaine, Win 35,428 and 30,065-2) and (+)-amphetamine. Br J Pharmacol 73:843–852

  22. Johanson CE, Fishman MW (1989) Pharmacology of cocaine related to its abuse, Pharmacol Rev 41:3–53

  23. Joyce EM, Iversen SD (1984) Dissociable effects of 6-OHDA induced lesions of neostriatum on anorexia, locomotor activity and stereotypy, the role of behavioral competition. Psychopharmacology 83:358–366

  24. Katz JL (1982) Rate-dependent effect ofd- orl-amphetamine on schedule controlled responding in pigeons and squirrel monkeys. Neuropharmacology 21:235–242

  25. Kelley AE, Lang CG (1989) Effects of GBR 12909, a selective dopamine uptake inhibitor, on motor activity and operant behavior in the rat. Eur J Pharmacol 167:385–395

  26. Kelley AE, Winnock M, Stinus L (1986) Amphetamine, apomorphine and investigatory behavior in the rat: Analysis of the structure and pattern of responses. Psychopharmacology 88:66–74

  27. Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi, and corpus striatum. Brain Res 94:507–522

  28. Kleven MS, Anthony EW, Woolverton W (1990) Pharmacological characterization of the discriminative stimulus effects of cocaine in rhesus monkeys. J Pharmacol Exp Ther 254:312–317

  29. Kornetsky C, Esposito RU, Mclean S, Jacobson O (1979) Intracranial self-stimulation thresholds. A model for the hedonic effects of drugs of abuse. Arch Gen Psychiatry 36:289–292

  30. Lyon M, Robbins TW (1975) The action of central nervous system stimulant drugs: a general theory concerning amphetamine effects. In: Essman W, Valzelli L (eds) Current developments in psychopharmacology, Vol. 2. Spectrum, New York, 79–163

  31. Mandelbrot B (1977) Fractals: form, chance and dimension. Freeman, San Francisco

  32. Moghaddam B, Bunney BS (1989) Differential effect of cocaine on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens: comparison to amphetamine. Synapse 4:156–161

  33. Morency MA, Beninger RJ (1986) Dopaminergic substrates of cocaine-induced place conditioning. Brain Res 399:33–41

  34. Paulus MP, Geyer MA (1991a) A temporal and spatial scaling hypothesis for the behavioral effects of psychostimulants. Psychopharmacology 104:6–15

  35. Paulus MP, Geyer MA (1991b) A scaling approach to find order parameters quantifying the effects of dopaminergic agents on unconditioned motor activity in rats. Prog Neuropsychopharmacol Biol Psychiatry 15:903–919

  36. Paulus MP, Geyer MA (1992) The effects of MDMA and other methylenedioxy substituted phenylalkylamines on the structure of rat locomotor activity. Neuropsychopharmacology 7:15–31

  37. Paulus MP, Geyer MA (1993) Quantitative assessment of the microstructure of rat behavior: I.f(d), The extension of the scaling hypothesis. Psychopharmacology (in press)

  38. Pickens R, Thompson T (1968) Cocaine-reinforced behavior in rats: effects of reinforcement magnitude and fixed-ratio size. J Pharmacol Exp Ther 161:122–129

  39. Randrup A, Munkvad I (1967) Stereotyped activity produced by amphetamine in several species and man. Psychopharmacology 11:300–310

  40. Rempel NL, Callaway CW, Geyer MA (1993) Serotonin-1B receptor activation mimics behavioral effects of presynaptic serotonin release. Neuropsychopharmacology 8:201–211

  41. Ritz MC, Lambs RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1224

  42. Robbins TW (1981) Behavioral determinants of drug action: rate-dependency revisited. In: Cooper SJ (ed) Theory in psychopharmacology, Vol. 1. Academic Press, New York, pp 1–63

  43. Robbins TW, Evenden JL (1985) Rate-independent approaches to the analysis of drug action. In: Lowe CF, Richelle M, Blackman DE, Bradshaw CM, (eds) Behaviour analysis and contemporary psychology. Lawrence Erlbaum Associates, London, pp 217–256

  44. Ruelle D (1989) Chaotic evolution and strange attractors: the statistical analysis of time series for deterministic nonlinear system. Cambridge University Press, New York.

  45. Sanger DJ, Blackman DE (1976) Rate-dependent effects of drugs: a review of the literature. Pharmacol Biochem Behav 4:73–83

  46. Scheel-Krueger J, Baestrup C, Nielson M, Golembiowska K, Mogilnicka E (1977) Cocaine: discussion on the role of dopamine in the biochemical mechanisms of action. In: Ellinwood EH, Kilbey MM (eds) Cocaine and other stimulants. Plenum, New York, pp 373–408

  47. Schiorring E (1971) Amphetamine induced selective stimulation of certain behaviour items with concurrent inhibition of others in an open-field test with rats. Behaviour 29:1–17

  48. Spyraki C, Fibiger HC, Phillips AG (1982) Cocaine-induced place preference: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203

  49. Stanley HE (1987) Introduction to phase transitions and critical phenomena. Oxford University Press, New York

  50. Ungerstedt U (1971) Aphagia and adipsia after 6-hydroxydopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 82[Suppl 367]:95–122

Download references

Author information

Correspondence to Martin P. Paulus.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Paulus, M.P., Callaway, C.W. & Geyer, M.A. Quantitative assessment of the microstructure of rat behavior: II. Distinctive effects of dopamine releasers and uptake inhibitors. Psychopharmacology 113, 187–198 (1993).

Download citation

Key words

  • Rat
  • Behavior
  • Microstructure
  • Dopamine releasers
  • Dopamine uptake inhibitors