Opioid receptor gene expression in dopamine transporter knock-out mice in adult and during development

Abstract

Dopamine transporter knock-out mice display locomotor hyperactivity due to increased extracellular striatal levels of dopamine. Hyperdopaminergic activity within this mesolimbic pathway is involved in the rewarding properties of morphine which are also increased in these mice. Due to the hyperdopaminergia, profound alterations in gene expression for dopamine receptors and neuropeptides are observed in the caudate putamen and nucleus accumbens. Here we investigated (1) the levels of μ-, δ- and κ-opioid receptors mRNAs in normal mice from gestational day 13 (G13) to adult, and (2) the adaptive changes in the expression of these receptors in mice lacking the dopamine transporter. Our results show that, in wild-type mice, μ-opioid receptor mRNA expression appears early during development (G13) with a homogeneous distribution that evolves towards a patchy distribution in adult. δ-Opioid receptor mRNA appears only at G17 and κ-opioid receptor mRNA is not observed before adulthood. The levels of δ-opioid receptor mRNA are not modified during development in knock-out mice compared to wild-type, but are increased in adult caudate putamen (+39%, P<0.05) and nucleus accumbens (+66%, P<0.05) at a time when these receptors are believed to be functional. The μ- and κ-opioid receptors mRNA levels are not modified in the adult knock-out mice. In addition, we observed no differences in any opioid receptor mRNA level in dopamine transporter knock-out mice during prenatal ontogeny compared to wild-type. Our results constitute a detailed neuroanatomical description of opioid receptor mRNA expression from the time of their appearance during prenatal development until adulthood. Furthermore, we show here that chronic constitutive hyperdopaminergia only affects δ-opioid receptor mRNA levels in adult. Even if the propensity of knock-out mice to show increased rewarding properties to morphine seems to be mainly due to the substantial and further increase in hyperdopaminergic activity following drug treatment, the involvement of increased δ-opioid receptor mRNA levels in this behavior remains to be elucidated.