μ Opioid receptor coupling to Gi/o proteins increases during postnatal development in rat brain

mu Opioid receptors are densely expressed within rat striatum and are concentrated in anatomically discrete patches called striosomes. The density of striosomal mu receptors remains relatively constant during postnatal development, but little is known about their functional maturation. We examined the extent of G protein coupling by mu opioid receptors in rat brain during development, focusing on striosomes within the striatum because of receptor density. The mu receptors were quantified using [H-3][D-Ala(2), N-Me-Phe(4),Gly(5)-ol]-enkephalin ( DAMGO) autoradiography. Adjacent sections were analyzed for DAMGO-stimulated guanosine 5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gamma S) binding to assess mu receptor activation of G(i/o) proteins. Striosomal mu receptor expression increased only slightly between postnatal day 5 and adult. In contrast, mu receptor-stimulated [S-35] GTP gamma S binding increased from 0.13 to 2.6 fmol/mg tissue over the same period, a 20-fold difference. The ratio of specific DAMGO-stimulated [S-35] GTP gamma S binding to [H-3] DAMGO binding, representing the relative number of G proteins activated per receptor, increased 19-fold between postnatal day 5 and adult. Similar patterns were observed throughout the striatum and other brain regions such as the nucleus accumbens, although the extent of change varied from region to region. These data indicate that mu opioid receptors exhibit enhanced function in the adult rat brain compared with the neonate. These data also suggest that this increase in G protein coupling is developmentally regulated and that in the developing rat brain the density of mu opioid receptor expression may not necessarily correlate with receptor activation of G proteins.