Direct Facilitatory Role of Paragigantocellularis Neurons in Opiate Withdrawal-Induced Hyperactivity of Rat Locus Coeruleus Neurons: An In Vitro Study

Studies have shown that following opiate withdrawal, the spontaneous discharge rate of locus coeruleus (LC) neurons remarkably increases. Combination of intrinsic mechanisms with extrinsic excitatory modulations mediates the withdrawal-induced hyperactivity of LC neurons. The nucleus paragigantocell...

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Bibliographic Details
Published in:PloS one 2015-07, Vol.10 (7), p.e0134873-e0134873
Main Authors: Kaeidi, Ayat, Azizi, Hossein, Javan, Mohammad, Ahmadi Soleimani, S Mohammad, Fathollahi, Yaghoub, Semnanian, Saeed
Format: Article
Language:English
Subjects:
Analgesics, Opioid - adverse effects
Animals
Brain
Brain slice preparation
Discharge
Excitation
Hyperactivity
In Vitro Techniques
Loci
Locus coeruleus
Locus Coeruleus - physiopathology
Male
Medulla Oblongata - physiopathology
Membrane potential
Membrane Potentials
Neurons
Neurons - physiology
Nucleus paragigantocellularis
Rats
Rats, Wistar
Substance Withdrawal Syndrome - physiopathology
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Summary:Studies have shown that following opiate withdrawal, the spontaneous discharge rate of locus coeruleus (LC) neurons remarkably increases. Combination of intrinsic mechanisms with extrinsic excitatory modulations mediates the withdrawal-induced hyperactivity of LC neurons. The nucleus paragigantocellularis (PGi) provides the main excitatory inputs to LC and plays a pivotal role in opiate withdrawal. In the present study the direct facilitatory role of PGi on opiate withdrawal-induced hyperactivity of LC neurons was investigated using a newly developed brain slice, containing both LC and PGi. HRP retrograde neuronal tracing was used to verify the existence of both LC and PGi neurons in the developed slice. The spontaneous discharge rate (SDR), resting membrane potential (RMP) and spontaneous excitatory post-synaptic currents (sEPSCs) were recorded in LC neurons using whole cell patch clamp recording. Results showed that the net SDR and the net RMP of LC neurons in slices containing both LC and PGi neurons are significantly higher than slices lacking intact (uncut) PGi inputs. Also, the frequency of sEPSCs in those LC neurons receiving PGi inputs significantly increased compared to the slices containing no intact PGi inputs. Altogether, our results propose that increase in PGi-mediated excitatory transmission might facilitate the opiate withdrawal-induced hyperactivity of LC neurons.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0134873