Crucial role of feedback signals from prelimbic cortex to basolateral amygdala in the retrieval of morphine withdrawal memory

Song, Jiaojiao; Shao, Da; Guo, Xinli; Zhao, Ying; Cui, Dongyang; Ma, Qianqian; Sheng, Huan; Ma, Lan; Lai, Bin; Chen, Ming; Zheng, Ping

doi:10.1126/sciadv.aat3210

Cited by 35 publications

(30 citation statements)

References 38 publications

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“…Mice were treated with morphine (Shenyang No.1 Pharmaceutical Factory, China), as described before (Song et al, 2019). Morphine dependence was induced in mice by repeated intraperitoneal injections of morphine twice daily at 08.00 AM and 19.00 PM.…”

Section: Chronic Morphine Treatmentmentioning

confidence: 99%

Activity in projection neurons from prelimbic cortex to the PVT is necessary for retrieval of morphine withdrawal memory

Chu

et al. 2021

Cell Reports

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Section: Chronic Morphine Treatmentmentioning

confidence: 99%

Activity in projection neurons from prelimbic cortex to the PVT is necessary for retrieval of morphine withdrawal memory

Chu

et al. 2021

Cell Reports

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“…Similar with fear, aversion is involved in generalization and extinction 29,30,31 . To explore generalization formation and extinction processes in visual aversion, we designed a task using the highly similar dynamic and static stripe images referring to previous studies 32,33,34,35 (Fig. 2d).…”

Section: Ms Cholinergic Neuron Supports Rapid Generalization Formation and Extinction Of Visual Aversionmentioning

confidence: 99%

“…Aversion generalization task. The task protocol was made referring to previous studies 32,33,34,35 . The same two-chamber apparatus was used in aversion generalization task.…”

Section: Behavioral Protocolsmentioning

confidence: 99%

A Cholinergic Medial Septum Input to Medial Habenula Mediates Generalization Formation and Extinction of Visual Aversion

Tang

Han

et al. 2021

SSRN Journal

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Generalization formation and extinction of aversion are associated with affective disorders, but little is known about underlying mechanisms. Here, we established a novel procedure for induction of visual aversion by dynamic stripe images on digital screens in mice. We found that decreased activity of medial septum (MS) cholinergic neurons led to generalization aversion loss, but didn't affect its extinction. We identified a new projection from MS cholinergic neurons to medial habenula (MHb), and found that inhibiting MS→MHb cholinergic circuit disrupted generalization formation, while activating this circuit damaged extinction. The further studies showed that blockade of M1 mAChRs rather than α4β2 and α7 nAChRs on downstream glutamatergic neurons that corelease glutamate and acetylcholine blunted generalization enhancement and extinction deficit caused by activation of MS→MHb circuits. These findings reveal that MS→MHb cholinergic circuit modulates generalization formation and extinction of aversion, providing new insights on affective disorders such as PTSD and anxiety disorders.

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“…These studies used the tasks of drug self-administration [ 4 ] and conditioned place preference (CPP) [ 5 ] to induce craving and relapse behaviors. However, little research demonstrated the aversive effect induced by abused drugs, and this line of research often uses conditioned taste aversion (CTA) [ 6 ] or conditioned place aversion (CPA) [ 7 ] tasks to imitate avoiding drug-taking behaviors. In contrast to the reward, the abused drug’s aversive property is also crucial for drug dependence.…”

Section: Introductionmentioning

confidence: 99%

The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

Liou

et al. 2021

JCM

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A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.

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Crucial role of feedback signals from prelimbic cortex to basolateral amygdala in the retrieval of morphine withdrawal memory

Abstract: The interaction of the basolateral amygdala and prelimbic cortex plays a crucial role in the reactivation of addiction memory.

Cited by 35 publications

References 38 publications

Activity in projection neurons from prelimbic cortex to the PVT is necessary for retrieval of morphine withdrawal memory

Activity in projection neurons from prelimbic cortex to the PVT is necessary for retrieval of morphine withdrawal memory

A Cholinergic Medial Septum Input to Medial Habenula Mediates Generalization Formation and Extinction of Visual Aversion

The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

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