ONTOGENY OF NIGROSTRIATAL DOPAMINE NEURON AUTORECEPTORS - IONTOPHORETIC STUDIES

This study characterized somatodendritic dopamine (DA) autoreceptors o n nigral DA-containing neurons during postnatal development in chloral hydrate-anesthetized rats. Antidromically activated nigrostriatal DA (NSDA) neurons from 2-week-old animals were found to be less sensitive to the inhibitory effects of cumulative i.v. doses (1-32 mu g/kg) of the DA agonists apomorphine (D-2/D-3/D-1) and quinpirole (D-2/D-3) tha n those from adults. The age-dependent difference in DA agonist sensit ivity was found to be of significantly greater magnitude for apomorphi ne than for quinpirole. When a single i.p. dose (64 mu g/kg) of apomor phine that elicits a moderate level of inhibition was administered, ho wever, no significant differences between the sensitivity of 2-week-ol d and adult NSDA neurons were found. In iontophoretic studies, no age- dependent (1, 2 and 4 week-olds and adults) differences in nigral DA n euron sensitivity to the inhibitory effects of apomorphine, quinpirole and the D-3/D-2 agonist, 7-hydroxy-dipropylaminotetralin HBr were fou nd. Iontophoretic studies with the DA antagonists, eticlopride (D-2/D- 3) and 7-chloro-8-hydroxy-3-methyl-1 -phenyl-2,3,4,5-tetrahydro-1H-3-b enzazepine (D-1), and i.v. studies with the DA agonists 1-phenyl-2,3,4 ,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (D-1) and nyl-2,3,4,5-tetra hydro-(1H)-3-benzazepine-7,8-diol (D-1) indicate that somatodendritic DA autoreceptors on 2-week-old NSDA neurons appear to be of tile D-2/D -3 subtype. These results suggest that functional adult-like somatoden dritic DA autoreceptors are present on nigral DA neurons during early postnatal development. Given the conflict between the iontophoretic an d i.v. results, however, the nature of any potential age-dependent dif ferences in somatodendritic autoreceptor sensitivity to DA agonists wi ll need to be examined further in vitro.