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NEUROPHARMACOLOGY

µ Opioid Receptor Coupling to G_i/o Proteins Increases during Postnatal Development in Rat Brain

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska

µ Opioid receptors are densely expressed within rat striatum and are concentrated in anatomically discrete patches called striosomes. The density of striosomal µ receptors remains relatively constant during postnatal development, but little is known about their functional maturation. We examined the extent of G protein coupling by µ opioid receptors in rat brain during development, focusing on striosomes within the striatum because of receptor density. The µ receptors were quantified using [³H][D-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (DAMGO) autoradiography. Adjacent sections were analyzed for DAMGO-stimulated guanosine 5'-O-(3-[³⁵S]thio)triphosphate ([³⁵S]GTPS) binding to assess µ receptor activation of G_i/o proteins. Striosomal µ receptor expression increased only slightly between postnatal day 5 and adult. In contrast, µ receptor-stimulated [³⁵S]GTPS 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 [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 µ 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 µ opioid receptor expression may not necessarily correlate with receptor activation of G proteins.

Address correspondence to: Dr. L. Charles Murrin, 985800 Nebraska Medical Center, Omaha, NE 68198-5800. E-mail: cmurrin{at}unmc.edu