Quantitative assessment of the microstructure of rat behavior: II. Distinctive effects of dopamine releasers and uptake inhibitors.
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 with d-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/kg d-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 of d-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.
Laboratory of Biological Dynamics and Theoretical Medicine, School of Medicine, University of California, San Diego, La Jolla 92093-0804.
M P
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Paulus
C W
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Callaway
M A
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Geyer
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D009627:Nomifensine; C043425:vanoxerine; D003042:Cocaine; D003913:Dextroamphetamine