UNILATERAL NEONATAL INTRACEREBROVENTRICULAR 6-HYDROXYDOPAMINE ADMINISTRATION IN RATS .2. EFFECTS ON EXTRACELLULAR MONOAMINE, ACETYLCHOLINE AND ADENOSINE LEVELS MONITORED WITH IN-VIVO MICRODIALYSIS

6-hydroxydopamine (6-OHDA, 100 mu g in 5 mu l) was injected into the right ventricle of 3-day-old Sprague Dawley rats in order to produce a unilateral dopamine (DA) lesion. At adult stage, the rats were implanted with microdialysis probes into the left and right striata. On the injected side, basal extracellular levels of DA were reduced by >65%, as compared to the contralateral side or to the levels found in vehicle-injected rats. Extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were reduced by >95%, while acetylcholine (ACh) was decreased by >50%. d-Amphetamine (2 mg/kg SC) produced a 10-fold increase in extracellular DA levels in the striatum contralateral to the 6-OHDA-injected side, while on the ipsilateral side, DA levels were not affected by d-amphetamine. d-Amphetamine produced an increase (>2 fold) in extracellular ACh levels, on both ipsilateral and con tralateral sides. Choline and adenosine levels were unaffected by any of the experimental conditions. Thus, neonatal unilateral ICV administration of 6-OHDA produced an ipsilateral decrease in striataI extracellular DA, DOPAC and HVA levels, compared to the contralateral side. A reduction of extracellular ACh levels was also observed on the 6-OHDA-injected side. The DA releasing effect of d-amphetamine was abolished on the 6-OHDA-injected side, but not that on ACh levels, indicating that striatal DA and ACh d-amphetamine-induced release are produced by independent mechanisms in the neonatally unilateral 6-OHDA-treated animals. As a whole the present study gives evidence showing that neonatal unilateral ICV treatment with 6-OHDA produces a predominantly unilateral lesion of the mesencephalic DA systems.