Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior
Drug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending o...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.996379/full |
| _version_ | 1818083101656481792 |
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| author | Yanghui Zhang Haoxian Li Ting Hu Ting Hu Zijin Zhao Zijin Zhao Qing Liu Qing Liu Haoyu Li Haoyu Li |
| author_facet | Yanghui Zhang Haoxian Li Ting Hu Ting Hu Zijin Zhao Zijin Zhao Qing Liu Qing Liu Haoyu Li Haoyu Li |
| author_sort | Yanghui Zhang |
| collection | DOAJ |
| description | Drug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending on the basolateral amygdala (BLA). Pharmacology or behavior treatment that disrupts the reconsolidation can effectively attenuate drug-seeking in addicts. Here, we hypothesized that heroin-memory reconsolidation requires cAMP-dependent protein kinase A (PKA) of BLA based on the fundamental effect of PKA in synaptic plasticity and memory process. After 10 days of acquisition, the rats underwent 11 days of extinction training and then received the intra-BLA infusions of the PKA inhibitor Rp-cAMPS at different time windows with/without a reactivation session. The results show that PKA inhibitor treatment in the reconsolidation time window disrupts the reconsolidation and consequently reduces cue-induced reinstatement, heroin-induced reinstatement, and spontaneous recovery of heroin-seeking behavior in the rats. In contrast, there was no effect on cue-induced reinstatement in the intra-BLA infusion of PKA inhibitor 6 h after reactivation or without reactivation. These data suggest that PKA inhibition disrupts the reconsolidation of heroin-associated memory, reduces subsequent drug seeking, and prevents relapse, which is retrieval-dependent, time-limited, and BLA-dependent. |
| first_indexed | 2024-12-10T19:32:39Z |
| format | Article |
| id | doaj.art-59cd81a58bbc4ab0bd63b6aae54c23d7 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T19:32:39Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-59cd81a58bbc4ab0bd63b6aae54c23d72022-12-22T01:36:12ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-08-011610.3389/fncel.2022.996379996379Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behaviorYanghui Zhang0Haoxian Li1Ting Hu2Ting Hu3Zijin Zhao4Zijin Zhao5Qing Liu6Qing Liu7Haoyu Li8Haoyu Li9Center of Medical Genetics, Jiangmen Maternity and Child Health Care Hospital, Jiangmen, ChinaCenter of Medical Genetics, Jiangmen Maternity and Child Health Care Hospital, Jiangmen, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaThe Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaThe Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaThe Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, ChinaThe Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha, ChinaDrug abuse is considered a maladaptive pathology of emotional memory and is associated with craving and relapse induced by drug-associated stimuli or drugs. Reconsolidation is an independent memory process with a strict time window followed by the reactivation of drug-associated stimulus depending on the basolateral amygdala (BLA). Pharmacology or behavior treatment that disrupts the reconsolidation can effectively attenuate drug-seeking in addicts. Here, we hypothesized that heroin-memory reconsolidation requires cAMP-dependent protein kinase A (PKA) of BLA based on the fundamental effect of PKA in synaptic plasticity and memory process. After 10 days of acquisition, the rats underwent 11 days of extinction training and then received the intra-BLA infusions of the PKA inhibitor Rp-cAMPS at different time windows with/without a reactivation session. The results show that PKA inhibitor treatment in the reconsolidation time window disrupts the reconsolidation and consequently reduces cue-induced reinstatement, heroin-induced reinstatement, and spontaneous recovery of heroin-seeking behavior in the rats. In contrast, there was no effect on cue-induced reinstatement in the intra-BLA infusion of PKA inhibitor 6 h after reactivation or without reactivation. These data suggest that PKA inhibition disrupts the reconsolidation of heroin-associated memory, reduces subsequent drug seeking, and prevents relapse, which is retrieval-dependent, time-limited, and BLA-dependent.https://www.frontiersin.org/articles/10.3389/fncel.2022.996379/fullreconsolidationheroinPKABLAdrug-seeking |
| spellingShingle | Yanghui Zhang Haoxian Li Ting Hu Ting Hu Zijin Zhao Zijin Zhao Qing Liu Qing Liu Haoyu Li Haoyu Li Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior Frontiers in Cellular Neuroscience reconsolidation heroin PKA BLA drug-seeking |
| title | Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior |
| title_full | Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior |
| title_fullStr | Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior |
| title_full_unstemmed | Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior |
| title_short | Disrupting reconsolidation by PKA inhibitor in BLA reduces heroin-seeking behavior |
| title_sort | disrupting reconsolidation by pka inhibitor in bla reduces heroin seeking behavior |
| topic | reconsolidation heroin PKA BLA drug-seeking |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.996379/full |
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