DELAYED PLASTICITY OF THE MESOLIMBIC DOPAMINE SYSTEM FOLLOWING NEONATAL 6-OHDA LESIONS

In this study, we determined the ontogenetic profile (at postnatal day s 7, 14, 35, and 90) of tyrodine hydroxylase (TH) mRNA in the ventral mesencephalon, and the levels of TH immunoreactivity (TH-IR) and dopam ine (DA) transporter (DAT) sites in the striatum of rats that had rece ived intrastriatal 6-hydroxy dopamine (6-OHDA) or vehicle lesions on d ay of birth (DO) or postnatal day 1 (P1). TH-IR was significantly decr eased in all quadrants of the caudate-putamen at all time points, whil e TH-LR in the nucleus accumbens was unchanged, as compared to control s. Relative to the earliest time point (P7 lesion group), TH-IR recove red significantly in the medial. caudate-putamen (CPu) of the P14, P35 and P90 6-OHDA-lesioned groups. Quantitative autoradiography of [H-3] -mazindol binding to DAT sites showed significant, lesion-induced loss es throughout the caudate-putamen of the 6-OHDA-lesioned groups at all time points and did not show appreciable recovery. Using in situ hybr idization, significant (P <.05) decreases in TH mRNA levels were found at all time points in the lateral and medial substantia nigra pars co mpacta of 6-OHDA-lesioned animals. TH mRNA levels in the rostral ventr al tegmental area (VTA), which were significantly decreased at P7, P14 and P35, returned to control levels at P90. TH mRNA levels in the cau dal VTA were unchanged through P35 and became significantly elevated a s compared to controls (+22%, P <.05) by P90. Thus, recovery of TH-IR in the medial caudate-putamen occurred prior to the elevation in level s of TH mRNA of the VTA. Our findings suggest that compensation exists in early development in certain subpopulations of mesostriatal DA neu rons that differs from that in the adult. (C) 1997 Wiley-Liss, Inc.