 Home > Active Ingredient News > Study of Nervous System > Neuron: Scientists reveal the neural mechanisms that induce social avoidance behavior after long-term withdrawal from analgesic addiction

Neuron: Scientists reveal the neural mechanisms that induce social avoidance behavior after long-term withdrawal from analgesic addiction

 Last Update: 2022-10-20
 Source: Internet
 Author: User

Tags

long saliva dna

long lidocaine injection

Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com

Click on the blue word to follow us

Opioids are widely used for analgesia, but they have serious negative effects
on drug dependence.
The sharp increase in lethal doses of opioids has clearly contributed to the "opioid crisis"
in the United States to some extent.
Long-term opioid withdrawal causes symptoms such as anhedonia, opioid seeking, and social avoidance, which further increases the risk of
relapse.

Kappa type opioid receptor (KOR) and its endogenous ligand dynorphins
.
Dynorphins exert analgesic effects
by activating KOR to regulate the release of neurotransmitters.
KOR antagonists play an important role in the treatment of negative emotions caused by depression and drug withdrawal, while KOR agonists cause negative emotions
such as social avoidance.

DORSAL (DR) SEROTONIN (5-HT) NEURONS AND VENTRAL TEGMENTAL (VTA) DOPAMINE (DA) NEURONS EXPRESS KOR
.
Dopamine type 1 receptor neurons in the nucleus accumbens (NAc) region are enriched to express dynorphins, receive input from DA and 5-HT neurons, and play a role
in social behavior.

On October 4, 2022, Robert C.
Malenka's research team in the Department of Psychiatric and Behavioral Sciences at Stanford University revealed that opioid withdrawal in the NAc region KOR is overactivated, and 5-HT release is reduced, causing social impairment
.

KOR activation mediates social impairment caused by opioid withdrawal

Mice showed social impairments such as reduced contact time with fellow mice and reduced social preference after 3 weeks of receiving escalating doses of morphine.

Injection of a long-acting KOR antagonist in the NAc shell region significantly relieves social disturbance
caused by long-term morphine withdrawal.

Further induction of apoptosis of dynastic neurons in the NAc shell region (referred to as NAc-Pdyn neurons) by viral vector tools does not affect the social disorders caused by long-term withdrawal of morphine, but after induction of apoptosis of dynastic neurons (referred to as DH-Pdyn neurons) in the dorsal nucleus region of the middle suture, the social disorders caused by long-term withdrawal of morphine can be blocked, which indicates that the dorsal nucleus of the middle suture, not the NAc shell, can be blocked, The release of dynorphins regulates social disturbances
caused by morphine withdrawal.

Figure 1: Social impairment caused by morphine withdrawal requires activation of KOR

Middle-suture dorsal dorsal dynorphins can regulate social disorders caused by withdrawal

Optogenetics significantly reduced the social behavior
of mice after activating DH-Pdyn neurons or DH-Pdyn neurons projecting into the NAc loop.
Simultaneous activation of DH-Pdyn neurons by injection of KOR antagonists in the NAc shell region promotes social behavior
in mice.

Immunofluorescence experiments have found that dynorphins in the DH region are hardly co-released with dopamine, but about half of the dynorphin neurons are co-labeled
with serotonin neurons.
Viral tracing experiments DH-Pdyn neurons project primarily to the dorsomedial shell region of the NAc region, while serotonin neurons or neurons that are co-labeled with DH-Pdyn neurons project to the entire shell and core region of the NAc region
.

Figure 2: Social impairment due to morphine withdrawal requires dorsal dorsal dorsal dorsal dynorphins

KOR reduces serotonin release causing withdrawal-related social disorders

Retrograde virus experiments found that the NAc region received input from serotonin neurons expressing KOR from DH region, and KOR on serotonin neurons was specifically knocked out to significantly block social disorders
caused by long-term morphine withdrawal.
But knocking out KOR on dopaminergic neurons did not affect social impairment
caused by long-term morphine withdrawal.

Normally, KOR agonists inhibit serotonin release
.
Serotonin fluorescent probe intensity was recorded through fiber optics, and serotonin release in the NAc shell region increased during socialization, while serotonin release decreased during socialization after long-term morphine withdrawal
.
Serotonin release in the NAc shell region increases during social interaction after knockout of KOR, while serotonin release remains increased
during social processes after long-term morphine withdrawal.

Figure 3: KOR reduces serotonin release and causes withdrawal-related social impairment

summary

In this paper, it was found that KOR activation after opioid withdrawal inhibits the release of serotonin in the NAc shell region, causing social avoidance behavior
.

【References】

1.
Pomrenze et al.
, Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal, Neuron (2022),

https://doi.
org/10.
1016/j.
neuron.
2022.
09.
024

The images in the article are from references

This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.