Patterns of rat behavior will be quantified based on techniques derived from nonlinear dynamical systems' analysis to assess the influence of drugs of abuse on the organization of behavioral sequences. Specifically, new mathematical approaches based on large fluctuation statistics and order parameter models will enable detailed analyses of behavioral sequences. Many drugs of abuse, particularly psychostimulants, profoundly alter the organization of behavioral sequences in addition to changing the amount of behavior. The development and validation of the theoretically driven measures will be based on evaluations of an existing data base of studies of psychostimulant effects on the sequential behavior of rats exploring a novel environment. In addition, selected studies are proposed to further test the validity of the theoretical approach. The project has 3 major aims: (1) To further develop the theoretical basis and mathematical tools to quantify behavioral organization, sensitive mathematical tools will be developed to assess behavioral sequences. The order parameter approach will be used to assess qualitative differences in behavioral subsets identified by distinct fluctuation spectra of both local dynamic entropies, S(h), and local spatial scaling exponents, f(d). Multi-dimensional fluctuation spectra functions will be developed to determine relationships between different local descriptors of behavior and to evaluate temporal influences on behavioral subsets. Analogies to statistical mechanics will be used to adapt the notion of a phase transition to behavior and to classify phase transitions in behavior. (2) To determine the influences of selected organismic, experiental, and neurobiological factors on normal and drug-induced behavioral organization. Using the Behavioral Pattern Monitor and the dependent measures from Aim 1, experiments will identify gender differences of psychostimulant's effects on behavioral organization and examine changes in behavioral organization associated with long- and short-term stressors. Neurobiological studies using neurotoxin lesions will seek to validate the theoretical developments by testing hypotheses about the anatomical substrates of dopaminergic influences on the behavioral topographies. (3) To identify predictors of enduring changes in behavioral organization induced by chronic psychostimulants. Behavioral sensitization after repeated administration of dopaminergic agents will be used as an experimental tool to identify long-term changes in behavioral organization and to test the utility of the concept of behavioral organization to predict individual differences of behavioral changes as a model for the susceptibility to drug use.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Shurtleff, David
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Ralph, R J; Paulus, M P; Fumagalli, F et al. (2001) Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knock-out mice: differential effects of D1 and D2 receptor antagonists. J Neurosci 21:305-13
Ralph, R J; Paulus, M P; Geyer, M A (2001) Strain-specific effects of amphetamine on prepulse inhibition and patterns of locomotor behavior in mice. J Pharmacol Exp Ther 298:148-55
Paulus, M P; Varty, G B; Geyer, M A (2000) The genetic liability to stress and postweaning isolation have a competitive influence on behavioral organization in rats. Physiol Behav 68:389-94
Varty, G B; Paulus, M P; Braff, D L et al. (2000) Environmental enrichment and isolation rearing in the rat: effects on locomotor behavior and startle response plasticity. Biol Psychiatry 47:864-73
Paulus, M P; Dulawa, S C; Ralph, R J et al. (1999) Behavioral organization is independent of locomotor activity in 129 and C57 mouse strains. Brain Res 835:27-36
Dulawa, S C; Grandy, D K; Low, M J et al. (1999) Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J Neurosci 19:9550-6
Paulus, M P; Geyer, M A; Sternberg, E (1998) Differential movement patterns but not amount of activity in unconditioned motor behavior of Fischer, Lewis, and Sprague-Dawley rats. Physiol Behav 65:601-6
Paulus, M P; Bakshi, V P; Geyer, M A (1998) Isolation rearing affects sequential organization of motor behavior in post-pubertal but not pre-pubertal Lister and Sprague-Dawley rats. Behav Brain Res 94:271-80