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Drug Res (Stuttg) 2022; 72(04): 209-214
DOI: 10.1055/a-1744-5868
Original Article

Administration of Orexin-A into the Rat Thalamic Paraventricular Nucleus Enhances the Naloxone Induced Morphine Withdrawal

Fatemeh Babaie
1   Department of Microbiology, Karaj Branch Islamic Azad University, Karaj, Iran
2   Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Masoumeh Kourosh-Arami
2   Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
,
Mona Farhadi
1   Department of Microbiology, Karaj Branch Islamic Azad University, Karaj, Iran
2   Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
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Abstract

Objective Orexin neuropeptides are implicated in physical dependence on opioids and expression of withdrawal symptoms in drug abuse. The paraventricular nucleus of the midline thalamus (PVT) has a high expression of orexin receptors. The current research studied the effect of orexin-A in the PVT area on the development of behavioral indices produced by morphine withdrawal in rats.

Methods Male Wistar rats weighing 250–300 gr were utilised. To produce drug dependence, morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) was injected at an interval of 24 hrs for 7 days. To assess the involvement of the orexin in withdrawal syndrome, we injected orexin-A (100 μM, 200 nl) into the PVT for 7 days before each morphine injection. On the day after the last injection of morphine, naloxone (2.5 mg/kg, i.p.) was injected to elicit the morphine withdrawal symptoms which were observed and checked for 25 min.

Results The results of the current research showed that the orexin-A in PVT enhances the severity of behavioral symptoms prompted by the injection of naloxone in drug-dependent rats.

Conclusions These observations imply that targeting the orexin receptors in PVT might exhibit a new therapeutic strategy for the future treatment of dependence.

Key words

Dependent rat - Morphine withdrawal - Orexin-A - Paraventricular nucleus


Publication History

Received: 08 September 2021

Accepted: 17 January 2022

Article published online:
06 April 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Watanabe T. et al. Involvement of noradrenergic system within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats. Psychopharmacology 2003; 170: 80-88
    CrossrefPubMedGoogle Scholar
  • 2 Dehpour A. et al. The effect of the serotonergic system on opioid withdrawal-like syndrome in a mouse model of cholestasis. Human Psychopharmacology: Clinical and Experimental 2000; 15: 423-428
    CrossrefPubMedGoogle Scholar
  • 3 Parvizpour A. et al. Repeated central administration of selegiline attenuated morphine physical dependence in rat. Pharmacological Reports 2013; 65: 593-599
    CrossrefPubMedGoogle Scholar
  • 4 Chartoff EH. et al. Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal. Journal of Neuroscience 2006; 26: 6450-6457
    CrossrefPubMedGoogle Scholar
  • 5 Bajo M. et al. Acute morphine alters GABAergic transmission in the central amygdala during naloxone-precipitated morphine withdrawal: role of cyclic AMP. Frontiers in integrative neuroscience 2014; 8: 45
    CrossrefPubMedGoogle Scholar
  • 6 Borgland SL. et al. Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine. Neuron 2006; 49: 589-601
    CrossrefPubMedGoogle Scholar
  • 7 Sharf R, Sarhan M, DiLeone RJ. Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell. Biological psychiatry 2008; 64: 175-183
    CrossrefPubMedGoogle Scholar
  • 8 De Lecea L. et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proceedings of the National Academy of Sciences 1998; 95: 322-327
    CrossrefPubMedGoogle Scholar
  • 9 Sakurai T. et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 1998; 92: 573-585
    CrossrefPubMedGoogle Scholar
  • 10 Mieda M, Tsujino N, Sakurai T. Differential roles of orexin receptors in the regulation of sleep/wakefulness. Frontiers in endocrinology 2013; 4: 57
    CrossrefPubMedGoogle Scholar
  • 11 Pittman QJ, Hatton JD, Bloom FE. Morphine and opioid peptides reduce paraventricular neuronal activity: studies on the rat hypothalamic slice preparation. Proceedings of the National Academy of Sciences 1980; 77: 5527-5531
    CrossrefPubMedGoogle Scholar
  • 12 Arami MK, Hajizadeh S, Semnanian S. Postnatal development changes in excitatory synaptic activity in the rat locus coeruleus neurons. Brain research 2016; 1648: 365-371
    CrossrefPubMedGoogle Scholar
  • 13 Arami MK. et al. Postnatal developmental alterations in the locus coeruleus neuronal fast excitatory postsynaptic currents mediated by ionotropic glutamate receptors of rat. Physiology and Pharmacology 2011; 14: 337-348
    PubMedGoogle Scholar
  • 14 Georgescu D. et al. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. Journal of Neuroscience 2003; 23 p 3106-3111
    CrossrefPubMedGoogle Scholar
  • 15 Peyron C. et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. Journal of Neuroscience 1998; 18: 9996-10015
    CrossrefPubMedGoogle Scholar
  • 16 Rezaei Z. et al. Orexin type-1 receptor inhibition in the rat lateral paragigantocellularis nucleus attenuates development of morphine dependence. Neuroscience Letters 2020; p 134875
    CrossrefPubMedGoogle Scholar
  • 17 Hsu DT. et al. Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood. Frontiers in behavioral neuroscience 2014; 8: 73
    PubMedGoogle Scholar
  • 18 Martin-Fardon R, Boutrel B. Orexin/hypocretin (Orx/Hcrt) transmission and drug-seeking behavior: is the paraventricular nucleus of the thalamus (PVT) part of the drug seeking circuitry?. Frontiers in behavioral neuroscience 2012; 6: 75
    CrossrefPubMedGoogle Scholar
  • 19 Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nature Reviews Neuroscience 2007; 8: 171-181
    CrossrefPubMedGoogle Scholar
  • 20 Fuertes G. et al. Changes in hypothalamic paraventricular nucleus catecholaminergic activity after acute and chronic morphine administration. European journal of pharmacology 2000; 388: 49-56
    CrossrefPubMedGoogle Scholar
  • 21 Niknia S. et al. Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy. Neuropeptides 2019; 73: 34-40
    CrossrefPubMedGoogle Scholar
  • 22 Paxinos G, Watson C. A stereotaxic atlas of the rat brain. New York: Academic; 1998
    Google Scholar
  • 23 Li Y. et al. Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology 2010; 212: 251-265
    CrossrefPubMedGoogle Scholar
  • 24 Rasmussen K. The role of the locus coeruleus and N-methyl-D-aspartic acid (NMDA) and AMPA receptors in opiate withdrawal. Neuropsychopharmacology 1995; 13: 295-300
    CrossrefPubMedGoogle Scholar
  • 25 Leung C, Dai S, Ogle C. Rapid induction of dependence to morphine in rats. Neuropharmacology 1986; 25: 305-307
    CrossrefPubMedGoogle Scholar
  • 26 Badawy AB, Evans C, Evans M. Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water. British journal of pharmacology 1982; 75: 485-491
    CrossrefPubMedGoogle Scholar
  • 27 Li Y. et al. Orexin-A acts on the paraventricular nucleus of the midline thalamus to inhibit locomotor activity in rats. Pharmacology Biochemistry and Behavior 2009; 93: 506-514
    CrossrefPubMedGoogle Scholar
  • 28 Maldonado R. et al. Role of different brain structures in the expression of the physical morphine withdrawal syndrome. Journal of Pharmacology and Experimental Therapeutics 1992; 261: 669-677
    PubMedGoogle Scholar
  • 29 Fadel J, Deutch A. Anatomical substrates of orexin–dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience 2002; 111: 379-387
    CrossrefPubMedGoogle Scholar
  • 30 Johnstone LE. et al. Local morphine withdrawal increases c-fos gene, Fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells. Journal of neuroscience 2000; 20: 1272-1280
    CrossrefPubMedGoogle Scholar
  • 31 Laorden ML. et al. Hypothalamic orexin-A neurons are involved in the response of the brain stress system to morphine withdrawal. PLoS One 2012; 7
    PubMedGoogle Scholar
  • 32 Kourosh-Arami M. et al. Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats. International Journal of Neuroscience 2022; 67-76
    CrossrefPubMedGoogle Scholar
  • 33 Kourosh-Arami M, Javan M, Semnanian S. Inhibition of orexin receptor 1 contributes to the development of morphine dependence via attenuation of cAMP response element-binding protein and phospholipase Cβ3. Journal of Chemical Neuroanatomy 2020; 101801
    CrossrefPubMedGoogle Scholar
  • 34 Kourosh-Arami M. et al. Phospholipase Cβ3 in the hippocampus may mediate impairment of memory by long-term blockade of orexin 1 receptors assessed by the Morris water maze. Life Sciences 2020; 257: 118046
    CrossrefPubMedGoogle Scholar
  • 35 Rosin DL. et al. Hypothalamic orexin (hypocretin) neurons express vesicular glutamate transporters VGLUT1 or VGLUT2. Journal of Comparative Neurology 2003; 465: 593-603
    CrossrefPubMedGoogle Scholar
  • 36 Soffin E. et al. SB-334867-A antagonises orexin mediated excitation in the locus coeruleus. Neuropharmacology 2002; 42: 127-133
    CrossrefPubMedGoogle Scholar
  • 37 Trujillo KA, Akil H. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 1991; 251: 85-87
    CrossrefPubMedGoogle Scholar
  • 38 Redmond DE. et al. Behavioral effects of stimulation of the nucleus locus coeruleus in the stump-tailed monkey Macaca arctoides. Brain research. 1976
    PubMedGoogle Scholar