The development, adaptation, and application of methods used in nonlinear dynamics to concrete biological data, specifically to analyse rat locomotor paths, is proposed. The long-range goals are first, a theoretical development of an approach to the application of ergodic theory and specifically symbolic dynamics to the characterization of biological systems and, second, a practical demonstration of the potential utility of this approach in the study of the exploratory behavior of rats. Complexity measures developed in the field of ergodic theory will be calculated from data obtained from detailed monitoring of the spatiotemporal patterns of rat locomotor and investigatory behaviors to describe a """"""""phase"""""""" of the animals' behavior within a given time frame. The investigation of transitions between phases similar to the study of phase transitions in non-equilibrium thermodynamics will be used to derive descriptors, e.g. critical exponents, appropriate for the construction of predictive models, which will be recruited from abstract dynamical systems with an empirically specified parameter set. Experimentally, drug-induced phase transitions will be studied, focussing on stimulant and """"""""designer"""""""" drugs of abuse, which may eventually serve as discriminators and help to constitute new classifiers of different behavioral states. The proposed experiments focus on three major aims: (1) to further develop measures derived from the theory of nonlinear dynamical systems and to sensitively adapt the measures to the particular biological system being studied, i.e. rat locomotor and investigatory behavior under the influence of amphetamine, cocaine, and MDMA (Ecstasy), using existing data from extensive experiments done with a multivariate Behavioral Pattern Monitor; (2) to elucidate dynamical changes of drug-induced behavior in critical dose ranges in order to demonstrate the hypothesized coexistence of several non-equilibrium steady states at the same dose; and (3) to use the complexity measures to assess the stability of the drug-induced states by systematic perturbations in different modalities (acoustical, optical, tactile, drugs, etc.). The resulting models of stability and transition scenarios of drug-induced states should lead to a further understanding of the dynamical aspects of the behavioral effects of drugs of abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA006325-01
Application #
3213000
Study Section
Special Emphasis Panel (SRCM (03))
Project Start
1990-03-01
Project End
1995-02-28
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
1
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Paulus, M P; Geyer, M A; Braff, D L (1996) Use of methods from chaos theory to quantify a fundamental dysfunction in the behavioral organization of schizophrenic patients. Am J Psychiatry 153:714-7
Paulus, M P; Geyer, M A; Braff, D L (1994) The assessment of sequential response organization in schizophrenic and control subjects. Prog Neuropsychopharmacol Biol Psychiatry 18:1169-85
Paulus, M P; Callaway, C W; Geyer, M A (1993) Quantitative assessment of the microstructure of rat behavior: II. Distinctive effects of dopamine releasers and uptake inhibitors. Psychopharmacology (Berl) 113:187-98
Paulus, M P; Geyer, M A (1993) Quantitative assessment of the microstructure of rat behavior: I, f(d), the extension of the scaling hypothesis. Psychopharmacology (Berl) 113:177-86
Rempel, N L; Callaway, C W; Geyer, M A (1993) Serotonin1B receptor activation mimics behavioral effects of presynaptic serotonin release. Neuropsychopharmacology 8:201-11
Geyer, M A; Paulus, M P (1992) Multivariate and nonlinear approaches to characterizing drug effects on the locomotor and investigatory behavior of rats. NIDA Res Monogr 124:203-35
Paulus, M P; Geyer, M A (1992) The effects of MDMA and other methylenedioxy-substituted phenylalkylamines on the structure of rat locomotor activity. Neuropsychopharmacology 7:15-31
Paulus, M P; Geyer, M A (1991) A temporal and spatial scaling hypothesis for the behavioral effects of psychostimulants. Psychopharmacology (Berl) 104:6-16
Paulus, M P; Geyer, M A (1991) A scaling approach to find order parameters quantifying the effects of dopaminergic agents on unconditioned motor activity in rats. Prog Neuropsychopharmacol Biol Psychiatry 15:903-19
France, C P; Woods, J H; Ornstein, P (1989) The competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 attenuates the rate-decreasing effects of NMDA in rhesus monkeys without producing ketamine-like discriminative stimulus effects. Eur J Pharmacol 159:133-9