Received for publication December 14, 2004.
Revised April 27, 2005.
Accepted for publication April 27, 2005.

Mu Opioid Receptor Coupling to G_i/o Proteins Increases During Postnatal Development in Rat Brain

Abstract

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 of 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. Mu receptors were quantified using [³H]DAMGO autoradiography. Adjacent sections were analyzed for DAMGO-stimulated [³⁵S]GTPS 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 [³⁵S]GTPS binding increased from 0.13 fmol/mg tissue to 2.6 fmol/mg tissue over the same period, a 20-fold difference. The ratio of specific DAMGO-stimulated [³⁵S]GTPS binding to [³H]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 to the neonatal brain. 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.

Key words: G protein coupled receptors, G proteins, mu opioid receptors, ontogeny, signal transduction, striatum