Elsevier

Brain Research

Volume 624, Issues 1–2, 8 October 1993, Pages 19-28
Brain Research

Autonomic areas of rat brain exhibit increased Fos-like immunoreactivity during opiate withdrawal in rats

https://doi.org/10.1016/0006-8993(93)90055-RGet rights and content

Abstract

We sought to identify the brain areas that might contribute to the increased autonomic activity seen during morphine withdrawal by mapping neuronal expression of c-fos protein (Fos) and Fos-related antigens. Rats were implanted with morphine pellets or placebo pellets over a 5 day regimen and injected on day 6 with either saline or naltrexone (100 mg/kg). After a standard PAP immunocytochemical protocol, Fos-like immunoreactivity (Fos-LIR) was observed in medullary nuclei including the NTS (nucleus of the solitary tract), caudal (CVL) and rostral ventrolateral medulla (RVL). Although some Fos-LIR was seen in these areas in control rats (either morphine-implanted, saline injected, or placebo-implanted, saline or naltrexone injected), a significantly higher number of Fos-LIR-positive cells in NTS, CVL and RVL were seen after morphine withdrawal. Large numbers of Fos-like immunoreactive cells were also seen in the A5 area, the parabrachial nuclei of the pons and the locus coeruleus. Increased Fos-LIR was also detected in the paraventricular nucleus of the hypothalamus and the amygdala of morphine withdrawn rats. The Fos-LIR was co-localized with tyrosine hydroxylase immunoreactivity in many of the cells in caudal and rostral ventrolateral medulla, A5 and locus coeruleus. These data support the conclusion that autonomic areas in brain and noradrenergic/adrenergic cells in these areas are activated during morphine withdrawal and may contribute to the autonomic symptoms of opiate withdrawal.

Reference (85)

  • EnnisM. et al.

    A potent excitatory input to the nucleus locus coeruleus from the ventrolateral medulla

    Neurosci. Lett.

    (1986)
  • GilbeyM.P. et al.

    The influence of the paraventriculo-spinal pathway, and oxytocin and vasopressin on sympathetic preganglionic neurones

    Brain Res.

    (1982)
  • GiovannelliL. et al.

    Oxytocin neurons in the rat hypothalamus exhibit c-fos immunoreactivity upon osmotic stress

    Brain Res.

    (1990)
  • GuyenetP.G.

    Central noradrenergic neurons: the autonomic connection

    Prog. Brain Res.

    (1991)
  • HassenA.H. et al.

    Mu-receptors and opioid cardiovascular effects in the NTS of rat

    Peptides

    (1982)
  • HassenA.H. et al.

    Delta versus mu receptors: cardiovascular and respiratory effects of opiate agonists microinjected into nucleus tractus solitarius of cats

    Regulatory Peptides

    (1982)
  • HassenA.H. et al.

    Cardiovascular responses to opioid agonists injected into the nucleus of tractus solitarius of anesthetized cats

    Life Sci.

    (1982)
  • HaywardM.D. et al.

    Induction of the c-fos proto-oncogene during opiate withdrawal in the locus coeruleus and other regions of rat brain

    Brain Res.

    (1990)
  • KoobG.F. et al.

    Neural substrates of opiate withdrawal

    Trends Neurosci.

    (1992)
  • LoewyA.D. et al.

    Serotonergic projections from the ventral medulla to the intermediolateral cell column in the rat

    Brain Res.

    (1981)
  • MillanM.J. et al.

    Vasopressin and oxytocin in the rat spinal cord: distribution and origins in comparison to [Met]enkephalin, dynorphin and related opioids and their irresponsiveness to stimuli modulating neurohypophyseal secretion

    Neuroscience

    (1984)
  • PiekutD.T. et al.

    Co-existence of CRF and vasopressin immunoreactivity in parvocellular paraventricular neurons of rat hypothalamus

    Peptides

    (1986)
  • PieriboneV.A. et al.

    Adrenergic and non-adrenergic neurons in the C1 and C3 areas project to locus coeruleus: a fluorescent double labeling study

    Neurosci. Lett.

    (1988)
  • PunnenS. et al.

    Blockade of cholinergic receptors in the C1 area abolishes hypertensive response to opiates in the A1 area of the ventrolateral medulla

    Brain Res.

    (1985)
  • RasmussenK. et al.

    Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesions of the nucleus paragigantocellularis

    Brain Res.

    (1989)
  • RuggieroD.A. et al.

    Central control of the circulation by the rostral ventrolateral reticular nucleus: anatomical substrates

  • SharpF.R. et al.

    c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress

    J. Neurosci.

    (1991)
  • SonnenbergJ.L. et al.

    Glutamate receptor agonists increase the expression of Fos, and AP-1 DNA binding activity in the mammalian brain

    J. Neurosci. Res.

    (1989)
  • StinusL. et al.

    Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal

    Neuroscience

    (1990)
  • StornettaR.L. et al.

    Naltrexone precipitated morphine withdrawal stimulates c-fos production in autonomic areas of rat brainstem and forebrain

    Soc. Neurosci. Abst.

    (1992)
  • SunM.-K. et al.

    Effects of vasopressin and other neuropeptides on rostral medullary sympathoexcitatory neurons in vitro

    Brain Res.

    (1989)
  • TuckerD.C. et al.

    Organization of central adrenergic pathways. I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord

    J. Comp. Neurol.

    (1987)
  • AboodL.G.

    Mechanisms of tolerance and dependence: an overview

    NIDA Res. Monogr.

    (1984)
  • AghajanianG.K.

    Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine

    Nature

    (1978)
  • Al MaskatiH.A. et al.

    Cardiovascular and motor components of the defense reaction elicited in rats by electrical and chemical stimulation in amygdala

    J. Autonomic Nervous System

    (1989)
  • BarabanS.C. et al.

    Respiratory control of sympathetic nerve activity during naloxone-preciptated morphine withdrawal in rats

    J. Pharmacol. Exp. Ther.

    (1993)
  • BenarrochE.E. et al.

    Neurons of the C1 area of rostral ventrolateral medullar mediate nucleus tractus solitarii hypertension

    Hypertension

    (1986)
  • CarterD.A. et al.

    Selective mediation of kappaopioid central cardiovascular effects by ascending noradrenergic pathways

    Exp. Brain Res.

    (1987)
  • CaversonM.M. et al.

    Organization of ventrolateral medullary afferents to the hypothalamus

  • CeccatelliS. et al.

    Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress

  • CirielloJ.

    Forebrain mechanisms in neurogenic hypertension

    Can. J. Physiol. Pharmacol.

    (1987)
  • CurranT. et al.

    Viral and cellular fos proteins are complexed with a 39,000-dalton cellular protein

    Mol. Cell. Biol.

    (1985)
  • Cited by (124)

    • Opioid withdrawal and memory consolidation

      2020, Neuroscience and Biobehavioral Reviews
    • The amygdalar opioid system

      2020, Handbook of Behavioral Neuroscience
      Citation Excerpt :

      A variety of studies using markers of neuronal activation (cFos, arc) in animals have indicated that naloxone-precipitated withdrawal or conditioned place aversion in morphine-dependent animals can activate the central and basolateral amygdala, especially the CM, IN, MEA, and both the dorsal and ventral BNST. None of these studies, however, identified the neuronal populations activated, although BLA activation was seen in GAD-negative neurons, suggesting this was specific to glutamatergic PNs (Frenois, Cador, Caille, Stinus, & Le Moine, 2002; Frenois, Stinus, Di Blasi, Cador, & Le Moine, 2005; Jin et al., 2005; Lucas et al., 2008; Lucas, Frenois, Cador, & Le Moine, 2012; Stornetta, Norton, & Guyenet, 1993). The most consistent activation during withdrawal is seen in the CM, where naloxone-precipitated withdrawal in morphine-dependent rats induced cFos specifically in ENKir neurons, but not CRFir neurons, in the CEA and the lateral BNST.

    View all citing articles on Scopus
    View full text