Research report
Postnatal development of multiple opioid receptors in rat brain

https://doi.org/10.1016/0165-3806(87)90226-4Get rights and content

Abstract

Recent studies have demonstrated that opioid receptors may be functional at early stages of ontogeny, and may modulate specific developmental functions. It is presently unknown, however, which particular opioid receptor subtype(s) may be involved. In the preent study, we have used selective radioligand binding conditions in combination with quantitative autoradiography to examine the ontogeny of μ-, ξ- and δ-opioid receptors in the developing rat brain. Membrane binding data indicate that the affinities of μ-, ξ- and δ- sites for radiolabeled drugs are similar in neonatal and adult rats. μ- And ξ-receptors are present in significant densities during early neonatal periods, while δ-receptors appear much later. Autoradiographic data indicate that μ- and ξ-receptors appear early in the development of several brain regions, including the neostriatum, olfactory tubercle and rostral midbrain, and later in other regions such as the thalamus and hypothalamus. Whereas the densities of ξ-binding sites remain relatively constant throughout development, there is a transient appearance and/or redistribution of μ-receptors in several brain areas. δ-Receptors are present in low densities in the basal forebrain at birth. The level of δ-receptor binding increases markedly during the third postnatal week in all brain areas examined. The early appearance of μ- and ξ-receptors during the ontogeny of the brain suggests that these receptors, at least in part, mediate the developmental actions of exogenous and endogenous opioids.

References (71)

  • B.H. Herman et al.

    Effects of morphine and naloxone on separation distress and approach attrachment: evidence for opiate mediation of social affect

    Pharmacol. Biochem. Behav.

    (1978)
  • H.I. Kornblum et al.

    Effects of morphine on DNA synthesis in neonatal rat brain

    Dev. Brain Res.

    (1987)
  • M.J. Kuhar et al.

    In vitro labeling receptor autoradiography: loss of label during ethanol dehydration and preparative procedures

    Brain Res.

    (1982)
  • R.A. Lahti et al.

    Properties of a selective kappa agonist U50488H

    Life Sci.

    (1982)
  • F.M. Leslie et al.

    Differential appearance of opiate receptor subtypes in neonatal rat brain

    Life Sci.

    (1982)
  • S.E. Loughlin et al.

    Postnatal development of opioid systems in rat brain

    Neuropeptides

    (1985)
  • S. McLean et al.

    Autoradiographic localization of μ- and δ-opiate receptors in the forebrain of the rat

    Brain Res.

    (1986)
  • K.P. Minneman et al.

    Classification and quantitation of beta-adrenergic receptor subtypes

    Biochem. Pharmacol.

    (1980)
  • P.B. Molinoff et al.

    Quantitative analysis of drug-receptor interactions. II. Determination of the properties of receptor subtypes

    Life Sci.

    (1981)
  • B.J. Morris et al.

    Autoradiographic localization in rat brain of κ opiate binding sites labelled by [3H]bremazocine

    Neuroscience

    (1986)
  • P.J. Munson et al.

    LIGAND: a versatile computerized approach for characterization of ligand binding systems

    Anal. Biochem.

    (1980)
  • J. Panksepp et al.

    Effects of β-chlornaltrexamine on separation distress in chicks

    Life Sci.

    (1982)
  • A. Pfeiffer et al.

    A subclassification of κ-sites in human brain by use of dynorphin 1–17

    Neuropeptides

    (1981)
  • R. Quirion et al.

    Comparative pharmacological properties and autoradiographic distributions of [3H]ethylketocyclazocine binding sites in rat and guinea pig brain

    Life Sci.

    (1983)
  • D. Tsang et al.

    Effect of antenatal exposure to opiates on the development of opiate receptors in rat brain

    Brain Res.

    (1980)
  • A. Tavani et al.

    Differential postnatal development of mu, delta, and kappa opioid binding sites in mouse brain

    Dev. Brain Res.

    (1985)
  • J.R. Unnerstall et al.

    Ontogeny of opiate binding sites in the hippocampus, olfactory bulb, and other regions of the rat forebrain by autoradiographic methods

    Dev. Brain Res.

    (1983)
  • P.L. Wood

    Multiple opiate receptors

  • I.S. Zagon et al.

    Perinatal methadone exposure and its influence on the behavioral ontogeny of rats

    Pharmacol. Biochem. Behav.

    (1978)
  • H. Akil et al.

    Endogenous opioids: biology and function

    Annu. Rev. Neurosci.

    (1984)
  • C.A. Altar et al.

    Computer-assisted video analyses of [3H]spiroperidol binding autoradiography

    J. Neurosci. Meth.

    (1984)
  • S.F. Atweh et al.

    Distribution and physiological significance of opioid receptors in the brain

    Br. Med. Bull.

    (1983)
  • F. Bloom

    The endorphins: a growing family of pharmacologically pertinent peptides

    Annu. Rev. Pharmacol. Toxicol.

    (1983)
  • W. Bowen et al.

    Interconverting mu and delta forms of the opiate receptor in rat striatal patches

  • E. Castanas et al.

    Interaction of opiates with opioid binding sites in the bovine adrenal medulla. II. Interaction with κ sites

    J. Neurochem.

    (1985)
  • Cited by (39)

    • Age-dependent effects of Κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate-putamen: An in vivo microdialysis study

      2010, Neuroscience
      Citation Excerpt :

      When the results of the present experiments are considered together, it appears that κ-opioid receptors in the CPu do not modulate dopaminergic functioning in a similar fashion during the preweanling period and in adulthood. The inability of U50,488 to block cocaine-induced dopamine overflow was not due to the late development of U50,488 binding sites, because κ-opioid receptor densities and mRNA levels are at approximately adult-like levels by PD 17 (Kornblum et al., 1987; Leslie and Loughlin, 1993; Georges et al., 1998). In adulthood, κ-opioid receptor stimulation activates voltage-dependent K+ channels and inhibits both adenylyl cyclase activity and voltage-dependent Ca2+ channels via inhibitory Gi and Go proteins (for reviews, see Childers, 1991; Minami and Satoh, 1995; Connor and Christie, 1999).

    View all citing articles on Scopus

    Present address: University of Hawaii, Bekesey Laboratory of Neurobiology, 1993 East-West Rd., Honolulu, HI 96822, U.S.A.

    View full text