title: Direct Facilitatory Role of Paragigantocellularis Neurons in Opiate Withdrawal-Induced Hyperactivity of Rat Locus Coeruleus Neurons: An In Vitro Study.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: Ayat
authors.initials: A
authors.lastname: Kaeidi
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Azizi
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: S Mohammad
authors.initials: SM
authors.lastname: Ahmadi Soleimani
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: Yaghoub
authors.initials: Y
authors.lastname: Fathollahi
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, PO Box 14115-331, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D000701:Analgesics, Opioid