Morphine withdrawal increases intrinsic excitability of oxytocin neurons in morphine‐dependent rats

To determine whether intrinsic mechanisms drive supraoptic nucleus oxytocin neuron excitation during morphine withdrawal, we calculated the probability of action potential (spike) firing with time after each spike for oxytocin neurons in morphine‐naïve and morphine‐dependent rats in vivo and measured changes in intrinsic membrane properties in vitro. The opioid receptor antagonist, naloxone, increased oxytocin neuron post‐spike excitability in morphine‐dependent rats; this increase was greater for short interspike intervals (< 0.1 s). Naloxone had similar, but smaller (P = 0.04), effects in oxytocin neurons in morphine‐naïve rats. The increased post‐spike excitability for short interspike intervals was specific to naloxone, because osmotic stimulation increased excitability without potentiating excitability at short interspike intervals. By contrast to oxytocin neurons, neither morphine dependence nor morphine withdrawal increased post‐spike excitability in neighbouring vasopressin neurons. To determine whether increased post‐spike excitability in oxytocin neurons during morphine withdrawal reflected altered intrinsic membrane properties, we measured the in vitro effects of naloxone on transient outward rectification (TOR) and after‐hyperpolarization (AHP), properties mediated by K+ channels and that affect supraoptic nucleus neuron post‐spike excitability. Naloxone reduced the TOR and AHP (by 20% and 60%, respectively) in supraoptic nucleus neurons from morphine‐dependent, but not morphine‐naïve, rats. In vivo, spike frequency adaptation (caused by activity‐dependent AHP activation) was reduced by naloxone (from 27% to 3%) in vasopressin neurons in morphine‐dependent, but not morphine‐naïve, rats. Thus, multiple K+ channel inhibition increases post‐spike excitability for short interspike intervals, contributing to the increased firing of oxytocin neurons during morphine withdrawal.

[1]  G. Leng,et al.  Temporal dissociation of the feedback effects of dendritically co-released peptides on rhythmogenesis in vasopressin cells , 2004, Neuroscience.

[2]  J. Clark,et al.  Increased expression of Ca2+/calmodulin-dependent protein kinase IIα during chronic morphine exposure , 2004, Neuroscience.

[3]  Gareth Leng,et al.  Phasic spike patterning in rat supraoptic neurones in vivo and in vitro , 2004, The Journal of physiology.

[4]  S. Reuss,et al.  Contribution of Ca2+‐Activated K+ Channels to Hyperpolarizing After‐Potentials and Discharge Pattern in Rat Supraoptic Neurones , 2004, Journal of neuroendocrinology.

[5]  G. Leng,et al.  Effects of Neurotensin on the Organization of Activity in Supraoptic Nucleus Cells in Virgin and Lactating Rats , 2004, Journal of neuroendocrinology.

[6]  C. Bourque,et al.  Autocrine feedback inhibition of plateau potentials terminates phasic bursts in magnocellular neurosecretory cells of the rat supraoptic nucleus , 2004, The Journal of physiology.

[7]  J. Russell,et al.  Cellular Mechanisms Underlying Neuronal Excitability during Morphine Withdrawal in Physical Dependence: Lessons from the Magnocellular Oxytocin System , 2004, Stress.

[8]  Hong-wei Dong,et al.  Organization of axonal projections from the anterolateral area of the bed nuclei of the stria terminalis , 2004, The Journal of comparative neurology.

[9]  G. Blackburn-Munro,et al.  The role of nitric oxide in morphine dependence and withdrawal excitation of rat oxytocin neurons , 2003, The European journal of neuroscience.

[10]  C. Sladek,et al.  Background and tandem‐pore potassium channels in magnocellular neurosecretory cells of the rat supraoptic nucleus , 2003, The Journal of physiology.

[11]  W. Armstrong,et al.  Changes in the Active Membrane Properties of Rat Supraoptic Neurones During Pregnancy and Lactation , 2002, Journal of neuroendocrinology.

[12]  I. Khalilov,et al.  Early sequential formation of functional GABAA and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus , 2002, The European journal of neuroscience.

[13]  Jianfeng Feng,et al.  Responses of Magnocellular Neurons to Osmotic Stimulation Involves Coactivation of Excitatory and Inhibitory Input: An Experimental and Theoretical Analysis , 2001, The Journal of Neuroscience.

[14]  N. Hussy,et al.  Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure , 2000, Progress in Neurobiology.

[15]  G. Leng,et al.  In Vivo Modulation of Post‐Spike Excitability in Vasopressin Cells by κ‐Opioid Receptor Activation , 2000, Journal of neuroendocrinology.

[16]  H. Meeren,et al.  Local Morphine Withdrawal Increases c-fos Gene, Fos Protein, and Oxytocin Gene Expression in Hypothalamic Magnocellular Neurosecretory Cells , 2000, The Journal of Neuroscience.

[17]  G. Leng,et al.  Opioid modulation of magnocellular neurosecretory cell activity , 2000, Neuroscience Research.

[18]  R. Elde,et al.  The kappa opioid receptor and dynorphin co-localize in vasopressin magnocellular neurosecretory neurons in guinea-pig hypothalamus , 2000, Neuroscience.

[19]  M. Connor,et al.  Continued morphine modulation of calcium channel currents in acutely isolated locus coeruleus neurons from morphine‐dependent rats , 1999, British journal of pharmacology.

[20]  Bourque,et al.  κ‐Opioid Receptor Activation Inhibits Post‐Spike Depolarizing After‐Potentials in Rat Supraoptic Nucleus Neurones In Vitro , 1999, Journal of neuroendocrinology.

[21]  S. Hestrin,et al.  Differences in the Properties of Ionotropic Glutamate Synaptic Currents in Oxytocin and Vasopressin Neuroendocrine Neurons , 1999, The Journal of Neuroscience.

[22]  Ludwig,et al.  Dendritic Release of Vasopressin and Oxytocin , 1998, Journal of neuroendocrinology.

[23]  S. Reuss,et al.  Components of after‐hyperpolarization in magnocellular neurones of the rat supraoptic nucleus in vitro , 1998, The Journal of physiology.

[24]  G Leng,et al.  κ-Opioid Regulation of Neuronal Activity in the Rat Supraoptic Nucleus In Vivo , 1998, The Journal of Neuroscience.

[25]  T. Ishii,et al.  Mechanism of calcium gating in small-conductance calcium-activated potassium channels , 1998, Nature.

[26]  G. Leng,et al.  Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat , 1998, The Journal of physiology.

[27]  N. Hussy,et al.  Vasopressin Regularizes the Phasic Firing Pattern of Rat Hypothalamic Magnocellular Vasopressin Neurons , 1998, The Journal of Neuroscience.

[28]  W. Armstrong,et al.  Reorganization of the Dendritic Trees of Oxytocin and Vasopressin Neurons of the Rat Supraoptic Nucleus during Lactation , 1998, The Journal of Neuroscience.

[29]  M. Ludwig,et al.  Local opioid inhibition and morphine dependence of supraoptic nucleus oxytocin neurones in the rat in vivo , 1997, The Journal of physiology.

[30]  G. Aston-Jones,et al.  Local opiate withdrawal in locus coeruleus in vivo , 1997, Brain Research.

[31]  G. Leng,et al.  The role of afferent inputs to supraoptic nucleus oxytocin neurons during naloxone-precipitated morphine withdrawal in the rat , 1997, Neuroscience.

[32]  C. Breton,et al.  Expression and region-specific regulation of the oxytocin receptor gene in rat brain. , 1997, Endocrinology.

[33]  J. Russell,et al.  Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats , 1997, Neuroreport.

[34]  J. Russell,et al.  Activation of oxytocin neurones by systemic cholecystokinin is unchanged by morphine dependence or withdrawal excitation in the rat. , 1996, The Journal of physiology.

[35]  T. Petrov,et al.  Activation of nitric oxide‐synthesizing neurones during precipitated morphine withdrawal , 1996, Neuroreport.

[36]  W. Armstrong,et al.  Changes in the Electrical Properties of Supraoptic Nucleus Oxytocin and Vasopressin Neurons during Lactation , 1996, The Journal of Neuroscience.

[37]  C. Bourque,et al.  Activity dependence and functional role of the apamin‐sensitive K+ current in rat supraoptic neurones in vitro. , 1996, The Journal of physiology.

[38]  H. Kaba,et al.  The action of oxytocin originating in the hypothalamic paraventricular nucleus on mitral and granule cells in the rat main olfactory bulb , 1996, Neuroscience.

[39]  E. Nestler,et al.  Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. , 1996, Molecular pharmacology.

[40]  J. Williams,et al.  Opioid Receptors and the Regulation of Ion Conductances , 1995, Reviews in the neurosciences.

[41]  G. Leng,et al.  Opioid tolerance and dependence in the magnocellular oxytocin system: a physiological mechanism? , 1995, Experimental physiology.

[42]  Stanley J. Watson,et al.  Immunohistochemical localization of the cloned μ opioid receptor in the rat CNS , 1995, Journal of Chemical Neuroanatomy.

[43]  B. Smith,et al.  Electrophysiological characteristics of immunochemically identified rat oxytocin and vasopressin neurones in vitro. , 1994, The Journal of physiology.

[44]  S. Oliet,et al.  Mechanosensitive channels transduce osmosensitivity in supraoptic neurons , 1993, Nature.

[45]  J. Russell,et al.  Oxytocin and vasopressin release in discrete brain areas after naloxone in morphine-tolerant and -dependent anesthetized rats: push-pull perfusion study , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  J. Russell,et al.  Contribution of the region anterior and ventral to the third ventricle to opiate withdrawal excitation of oxytocin secretion. , 1992, Neuroendocrinology.

[47]  G. Aston-Jones,et al.  Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  J. Russell,et al.  Release of Oxytocin into Blood and into Cerebrospinal Fluid Induced by Naloxone in Anaesthetized Morphine‐Dependent Rats: The Role of the Paraventricular Nucleus , 1991, Journal of neuroendocrinology.

[49]  G. Leng,et al.  Morphine actions on supraoptic oxytocin neurones in anaesthetized rats: tolerance after i.c.v. morphine infusion. , 1991, The Journal of physiology.

[50]  J. Russell,et al.  Opioid receptor subtypes in the supraoptic nucleus and posterior pituitary gland of morphine-tolerant rats , 1990, Neuroscience.

[51]  C. Bourque.  Transient calcium‐dependent potassium current in magnocellular neurosecretory cells of the rat supraoptic nucleus. , 1988, The Journal of physiology.

[52]  G. Leng,et al.  Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment. , 1988, The Journal of physiology.

[53]  J. Russell,et al.  Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones. , 1988, The Journal of physiology.

[54]  R. North,et al.  Cellular mechanisms of opioid tolerance: studies in single brain neurons. , 1987, Molecular pharmacology.

[55]  L. Renaud,et al.  Calcium-dependent potassium conductance in rat supraoptic nucleus neurosecretory neurons. , 1985, Journal of neurophysiology.

[56]  L. Renaud,et al.  Activity dependence of action potential duration in rat supraoptic neurosecretory neurones recorded in vitro. , 1985, The Journal of physiology.

[57]  M. Faludi,et al.  Oxytocin and a C-terminal derivative (Z-prolyl-d-leucine) attenuate tolerance to and dependence on morphine and interact with dopaminergic neurotransmission in the mouse brain , 1985, Neuropharmacology.

[58]  G. Kovacs,et al.  Effects of oxytocin and a derivative (Z-prolyl-d-leucine) on morphine tolerance/withdrawal are mediated by the limbic system , 1984, Behavioural Brain Research.

[59]  F. Dudek,et al.  Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism. , 1983, Science.

[60]  D. Lincoln,et al.  Electrophysiological evidence for the activation of supraoptic neurones during the release of oxytocin , 1974, The Journal of physiology.

[61]  G. Leng,et al.  Effects of the selective kappa-opioid agonist U50,488 upon the electrical activity of supraoptic neurones in morphine-tolerant and morphine-naive rats , 2004, Experimental Brain Research.

[62]  J T Williams,et al.  Cellular and synaptic adaptations mediating opioid dependence. , 2001, Physiological reviews.

[63]  M. G. Terenzi,et al.  Electrophysiological effects of oxytocin within the bed nuclei of the stria terminalis: influence of reproductive stage and ovarian steroids. , 1998, Progress in brain research.

[64]  黒川 清,et al.  Neurohypophysis : recent progress of vasopressin and oxytocin research : proceedings of the 1st Joint World Congress of Neurohypophysis and Vasopressin, Nasu, Tochigi, Japan, 16-21 July 1995 , 1995 .