QUANTITATIVE ASSESSMENT OF THE MICROSTRUCTURE OF RAT BEHAVIOR .2. 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 n omifensine (5.020.0 mg/kg), on the behavioral organization of movement s in an unconditioned motor paradigm were investigated in rats. The ex tended scaling hypothesis using the fluctuation spectrum of local spat ial scaling exponents was used to quantify the geometrical characteris tics of movements. The results reveal a qualitatively similar disrupti on of behavioral organization by lower doses of these drugs. Specifica lly, 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) exhibite d a reduced range in the fluctuation spectrum, reflecting a predominan ce of meandering movements with local spatial scaling exponents betwee n 1.3 and 1.7. This reduction was accompanied dynamically by a reduced predictability of movement sequences as measured by the dynamical ent ropy, 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 move ments that are interpreted as a combination of spatially extended and local perseveration. In contrast, high doses of 30.0 mg/kg GBR 12909 a nd 20.0 mg/kg nomifensine induced only local perseveration. High doses of damphetamine, cocaine, GBR 12909 and nomifensine reduced the dynam ical entropy, h, indicating an increased predictability of the movemen t sequences. These results suggest that the generic behavioral change induced by low doses of dopamine agonists is characterized by a reduce d variety of path patterns coupled with an increased variability in se quential movement sequences. The differential effects of higher doses of these drugs may be due to their influences on other neurotransmitte r systems or differential affinities for different dopamine subsystems .