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

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Abstract

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.

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References

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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)

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

Download references

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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). https://doi.org/10.1007/BF02245696

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  • DOI: https://doi.org/10.1007/BF02245696

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