Circadian rhythm influences naloxone induced morphine withdrawal and neuronal activity of lateral paragigantocellularis nucleus

Rahmati-Dehkordi, Fatemeh; Ghaemi-Jandabi, Masoumeh; Garmabi, Behzad; Semnanian, Saeed; Azizi, Hossein

doi:10.1016/j.bbr.2021.113450

Cited by 3 publications

(4 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to our recent study [ 30 ], electrophysiological recordings were initiated 2 h after the last morphine injection (on PND 70). First, the baseline activity of LPGi neurons was recorded for 10 min, then, naloxone injection was done (2 mg/kg, i.p.)…”

Section: Methodsmentioning

confidence: 94%

Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

2021

Self Cite

View full text Add to dashboard Cite

Introduction Adolescence is a critical period in brain development, and it is characterized by persistent maturational alterations in the function of central nervous system. In this respect, many studies show the non-medical use of opioid drugs by adolescents. Although this issue has rather widely been addressed during the last decade, cellular mechanisms through which adolescent opioid exposure may induce long-lasting effects are not duly understood. The present study examined the effect of adolescent morphine exposure on neuronal responses of lateral paragigantocellularis nucleus to naloxone in adult morphine-dependent rats. Methods Adolescent male Wistar rats (31 days old) received increasing doses of morphine (from 2.5 to 25 mg/kg, twice daily, s.c.) for 10 days. Control subjects were injected saline with the same protocol. After a drug-free interval (20 days), animals were rendered dependent on morphine during 10 days (10 mg/kg, s.c., twice daily). Then, extracellular single-unit recording was performed to investigate neural response of LPGi to naloxone in adult morphine-dependent rats. Results Results indicated that adolescent morphine treatment increases the number of excitatory responses to naloxone, enhances the baseline activity and alters the pattern of firing in neurons with excitatory responses in adult morphine-dependent rats. Moreover, the intensity of excitatory responses is reduced following the early life drug intake. Conclusion It seems that prolonged opioid exposure during adolescence induces long-lasting neurobiological changes in LPGi responsiveness to future opioid withdrawal challenges.

show abstract

Section: Methodsmentioning

confidence: 94%

Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, clock genes have long been implicated in addiction traits 75 , including opioid withdrawal [76][77][78][79][80][81] .…”

Section: Discussionmentioning

confidence: 99%

“…A human linkage scan of comorbid dependence on multiple substances, including opioids, identified significant linkage with a locus containing GABRA4 , GABRB1 , and CLOCK 74 . Furthermore, clock genes have long been implicated in addiction traits 75 , including opioid withdrawal 76–81 .…”

Section: Discussionmentioning

confidence: 99%

Atp1a2 and Kcnj9 are candidate genes underlying oxycodone behavioral sensitivity and withdrawal in C57BL/6 substrains

Goldberg,

Baskin,

Adla

et al. 2024

Preprint

View full text Add to dashboard Cite

Opioid use disorder is heritable, yet its genetic etiology is largely unknown. Analysis of addiction model traits in rodents (e.g., opioid behavioral sensitivity and withdrawal) can facilitate genetic and mechanistic discovery. C57BL/6J and C57BL/6NJ substrains have extremely limited genetic diversity, yet can show reliable phenotypic diversity which together, can facilitate gene discovery. The C57BL/6NJ substrain was less sensitive to oxycodone (OXY)-induced locomotor activity compared to the C57BL/6J substrain. Quantitative trait locus (QTL) mapping in an F2 cross identified a distal chromosome 1 QTL explaining 7-12% of the variance in OXY locomotor sensitivity and anxiety-like withdrawal in the elevated plus maze. We identified a second QTL for withdrawal on chromosome 5 near the candidate gene Gabra2 (alpha-2 subunit of GABA-A receptor) explaining 9% of the variance. Next, we generated recombinant lines from an F2 founder spanning the distal chromosome 1 locus (163-181 Mb), captured the QTL for OXY sensitivity and withdrawal, and fine-mapped a 2.45-Mb region (170.16-172.61 Mb). There were five striatal cis-eQTL transcripts in this region (Pcp4l1, Ncstn, Atp1a2, Kcnj9, Igsf9), two of which were confirmed at the protein level (KCNJ9, ATP1A2). Kcnj9, a.k.a., GIRK3, codes for a potassium channel that is a major effector of mu opioid receptor signaling. Atp1a2 codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows adaptations following chronic opioid administration. To summarize, we identified genetic sources of opioid behavioral differences in C57BL/6 substrains, two of the most widely and often interchangeably used substrains in opioid addiction research.

show abstract

“…However, neurobiological changes of dopaminergic neurons in the ventral tegmental area and nucleus accumbens (NAC) and noradrenergic neurons at the locus coeruleus (LC) may induce withdrawal symptoms. GABAergic mechanisms in the basal ganglia mediate anxiety, and the reduction in GABA activity induces fear and the spread of anxiety [ 8 ] .…”

Section: Introductionmentioning

confidence: 99%

The Investigation of Valproic Acid Administration on Learning, Social Interaction, and Depression Induced by Withdrawal Syndrome in Morphine-Depended Mice

Farhadi

Sabzalizadeh

Shamsara

et al. 2023

Preprint

View full text Add to dashboard Cite

Opioid addiction causes mood disorders and increases anxiety, depression, and cognitive impairment. Valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy. The animals were randomly divided into four groups (n=6). The control and valproic acid (VPA) groups were injected intraperitoneally with saline or valproic acid respectively. In the morphine sulfate (MOR) group, animals were injected subcutaneously with morphine sulfate. The MOR + VPA group received two injections of drugs, valproate, and morphine, as well as the VPA and MOR groups. All intraperitoneal and subcutaneous injections were done for 8 days. The animals were assessed on day 8 to behavioral tests. The administration of valproic acid and morphine was discontinued from day 8 and the animals entered spontaneous withdrawal syndrome. The behavioral tests were repeated on day 11. Results showed that PI% decreased in NORT in the VPA, MOR, and MOR + VPA groups compared with the CTL group in the withdrawal phase. The concomitant administration of VPA and morphine caused an increase in social interaction criteria in both the chronic and withdrawal phases. The decrease in immobility time of the VPA and MOR + VPA groups compared to the CTL group in the withdrawal phase was not statistically significant in the tail suspension test. The VPA can be assessed based on the degree of anxiety and depressive behaviors caused by the withdrawal syndrome. Therefore, reducing stress in rats during morphine withdrawal may be part of the beneficial effects of VPA in improving social relationships and depression indices.

show abstract

Circadian rhythm influences naloxone induced morphine withdrawal and neuronal activity of lateral paragigantocellularis nucleus

Cited by 3 publications

References 62 publications

Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

Prolonged morphine exposure during adolescence alters the responses of lateral paragigantocellularis neurons to naloxone in adult morphine dependent rats

Atp1a2 and Kcnj9 are candidate genes underlying oxycodone behavioral sensitivity and withdrawal in C57BL/6 substrains

The Investigation of Valproic Acid Administration on Learning, Social Interaction, and Depression Induced by Withdrawal Syndrome in Morphine-Depended Mice

Contact Info

Product

Resources

About