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Decrease of inhibitory synaptic currents of locus coeruleus neurons via orexin type 1 receptors in the context of naloxone-induced morphine withdrawal
- Source :
- The Journal of Physiological Sciences. 69:281-293
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Acute opioid withdrawal syndrome is a series of neurological symptoms caused by the abrupt cessation of the chronic administration of opioids such as morphine. The locus coeruleus (LC) in the brain stem receives a dense projection of orexinergic fibers from the hypothalamus and is a candidate site for the expression of the somatic aspects of morphine withdrawal. Previous studies have shown that orexin-A contributes to the behavioral symptoms of naloxone-induced morphine withdrawal, partly by reducing the activity of GABAergic neurons, suggesting that orexin-A may negatively modulate fast GABAergic neurotransmission during morphine withdrawal. We used whole-cell patch-clamp recordings of LC neurons in brainstem slices to investigate the effect of orexin-A on bicuculline-sensitive GABAergic inhibitory postsynaptic currents (IPSCs) during naloxone-induced morphine withdrawal. Male Wistar rats (P14-P21) were given morphine (20 mg/kg, i.p.) daily for seven consecutive days to create dependency on the drug. The application of naloxone (1 µM) to brain slices of morphine-treated rats reduced the amplitude of evoked IPSCs (eIPSCs) as well as spontaneous IPSCs (sIPSCs) frequency but did not change sIPSCs amplitude. Orexin-A (100 nM) significantly enhanced the suppressive effect of naloxone on eIPSCs amplitude and sIPSCs frequency but had no effect on the presence of the orexin type 1 receptor (OX1R) antagonist, SB-334867. Orexin-A alone had no significant effect on eIPSCs and sIPSCs in the absence of naloxone. In summary, our results show that orexin-A, via OX1R, potentiates the suppressive effect of naloxone on GABAergic IPSCs of LC neurons in morphine-treated rats. We conclude that orexins may have a critical role in regulating GABAergic neurotransmission to LC neurons during naloxone-induced morphine withdrawal.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Physiology
Narcotic Antagonists
Context (language use)
(+)-Naloxone
Bicuculline
Inhibitory postsynaptic potential
Synaptic Transmission
03 medical and health sciences
0302 clinical medicine
Orexin Receptors
Internal medicine
medicine
Animals
GABAergic Neurons
Rats, Wistar
Neurons
Morphine
Naloxone
business.industry
Synaptic Potentials
Rats
Substance Withdrawal Syndrome
Orexin
Analgesics, Opioid
030104 developmental biology
Endocrinology
nervous system
Hypothalamus
Locus coeruleus
GABAergic
Locus Coeruleus
Orexin Receptor Antagonists
business
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 18806562 and 18806546
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- The Journal of Physiological Sciences
- Accession number :
- edsair.doi.dedup.....bb927ec710052b006d7625236d2bf99b