DIFFERENTIAL ONTOGENY OF FUNCTIONAL DOPAMINE AND MUSCARINIC RECEPTORS MEDIATING PRESYNAPTIC INHIBITION OF NEUROTRANSMITTER RELEASE AND POSTSYNAPTIC REGULATION OF ADENYLATE-CYCLASE ACTIVITY IN RAT STRIATUM

To study the ontogeny of functional striatal dopamine (DA) D2 and muscarinic receptors we determined the first appearance of the inhibitory effects of activation of autoreceptors on neurotransmitter release and that of postsynaptic receptors on adenylate cyclase activity in striatal slices of rat foetuses and pups. On embryonic day 17 (E17), activation of D2 receptors with LY 171555 (1-mu-M) resulted in a 50% inhibition of the electrically evoked release of [H-3]DA from superfused striata, indicating that D2 autoreceptors are functional at that time. Stimulation of adenylate cyclase activity with the Da D1 agonist SK&F 38393 could also be determined in the striatum on E17. In contrast, inhibition of D1-stimulated adenylate cyclase activity through activation of postsynaptic D2 receptors did not occur until postnatal day 14 (P14), whereas activation of postsynaptic muscarinic receptors with oxotremorine (1-mu-M) resulted in 30% inhibition already on E17. Endogenous activation of muscarinic receptors with physostigmine (1-mu-M) was ineffective in the prenatal period, but its inhibitory effect on D1-stimulated adenylate cyclase increased strongly between P7 and P21. Inhibition of striatal [H-3]acetylcholine (ACh) release by activation of muscarinic receptors could not be determined until P7, because the release of the neurotransmitter was not measurable before that day. But on P7, oxotremorine and physostigmine (as well as the D2 receptor agonist LY 171555) reduced the electrically evoked release of [H-3]ACh from striatal slices. Taken together, these data show that there is a marked time difference between the coupling of D2 receptors and that of the D1 and muscarinic receptors to adenylate cyclase in the developing striatum. Furthermore, presynaptic D2 and muscarinic autoreceptors appear to be functional as soon as DA and ACh release from striatal slices can be detected.