Postnatal development of functional dopamine, opioid and tachykinin receptors that regulate acetylcholine release from rat neostriatal slices. Effect of 6-hydroxydopamine lesion

In the present work we have studied the postnatal development of functional dopamine, opioid and tachykinin receptors, which regulate cholinergic activity in the neostriatum. The release of endogenous acetylcholine from rat striatal slices was measured using a chemiluminescent method. We have observed that the inhibition mediated by dopamine through D₂ receptors was not detectable until postnatal day 10, whereas the inhibition mediated by opioid receptors was detectable at postnatal day 15 for δ-receptors ([D-Pen², D-Pen⁵]-enkephalin) and at postnatal day 21 for μ-receptors ([D-Ala², Gly(ol)⁵]-enkephalin). Excitatory effect mediated by tachykinins through NK₁ ([Sar⁹, Met(O2)¹¹]-Substance P), NK₂ ([Nle¹⁰]-Neurokinin A_4–10), or NK₃ (senktide) receptors was already detectable at postnatal day 5.

In order to examine the influence of dopamine in the development of tachykinin and opioid systems in the neostriatum, we induced dopamine deficiency by intraventricular injection of 6-hydroxydopamine at postnatal day 3. We observed an increase in senktide-evoked acetylcholine release at postnatal day 30. The effect produced by [Sar⁹, Met(O₂¹¹]-Substance P and [Nle¹⁰]-Neurokinin A_4–10 was not modified. Furthermore, at postnatal day 35, we could observed that the two opioid receptor agonists have no effect.

Our results show that dopamine, tachykinins and opioids are already able to mediate the modulation of acetylcholine release in early stages of development with a different pattern of postnatal development. Furthermore, the integrity of a dopaminergic system plays an important role in the functional development of the neostriatal cholinergic neurons which are differentially modulated by opioids or tachykinins.