Ontogeny of nigrostriatal dopamine neuron autoreceptors: iontophoretic studies

This study characterized somatodendritic dopamine (DA) autoreceptors on nigral DA-containing neurons during postnatal developmental 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 micrograms/kg) of the DA agonists apomorphine (D2/D3/D1) and quinpirole (D2/D3) than those from adults. The age-dependent difference in DA agonist sensitivity was found to be of significantly greater magnitude for apomorphine than for quinpirole. When a single i.p. dose (64 micrograms/kg) of apomorphine that elicits a moderate level of inhibition was administered, however, no significant differences between the sensitivity of 2-week-old and adult NSDA neurons were found. In iontophoretic studies, no age-dependent (1, 2 and 4 week-olds and adults) differences in nigral DA neuron sensitivity to the inhibitory effects of apomorphine, quinpirole and the D3/D2 agonist, 7-hydroxy-dipropylaminotetralin HBr were found. Iontophoretic studies with the DA antagonists, eticlopride (D2/D3) and 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (D1), and i.v. studies with the DA agonists 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (D1) and N-allyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (D1) indicate that somatodendritic DA autoreceptors on 2-week-old NSDA neurons appear to be of the D2/D3 subtype. These results suggest that functional adult-like somatodendritic DA autoreceptors are present on nigral DA neurons during early postnatal development. Given the conflict between the iontophoretic and i.v. results, however, the nature of any potential age-dependent differences in somatodendritic autoreceptor sensitivity to DA agonists will need to be examined further in vitro.