DOPAMINE D-2 RECEPTOR AUTORADIOGRAPHY WITH [H-3] YM-09151-2 REFLECTS BRAIN AND BEHAVIORAL ONTOGENY

1. Striatal D-2 receptor concentration (as determined by [H-3]-spipero ne binding to brain tissue homogenates) has been correlated, in F344 r ats, with a number of locomotor behaviors (e.g. response latency on co nditioned avoidance and decreased open field locomotion with apomorphi ne administration). 2. These data suggest that striatal D-2 receptor c oncentration may likewise correlate with spontaneous open field locomo tor activity since previous work has shown lower rates of locomotor ac tivity in 21-day old versus 30-day old F344 rats. 3. Using the techniq ue of in vitro receptor autoradiography to slide-mounted, coronal brai n sections, the authors studied the suitability of [H-3]-YM-09151-2 as a ligand for labeling D2 receptors in 21-day old and adult F344 rats. 4. Specific [H-3]-YM-09151-2 saturation binding accounted for 70-80% of the total bound ligand (K-d = 348 pM). Displacement experiments cor roborated previous findings using homogenates that [H-3]-YM 09151-2 bi nds specifically to the D-2 receptor. 5. Autoradiograms from 21-day ol d and adult brain sections demonstrated high grain densities in the ca udate-putamen, accumbens and olfactory tubercle. Diffuse specific bind ing was also observed in the cortex. Analysis of grain densities from areas corresponding to these brain regions revealed significantly less specific binding in 21-day old versus adult F344 rats. 6. These autor adiographic data are consistent with the expected increase in brain D- 2 receptor concentration during maturation and parallel observed chang es in open-field locomotor activity. Thus, [H-3]-YM 09151-2 appears to be a suitable ligand for autoradiographic labeling of the D-2 recepto r.