Glutamatergic Neurons in Ventral Pallidum Modulate Heroin Addiction Via Epithalamic Innervation in Rats

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2024 Feb 7

PMID 38326624

Authors

Ruo-Song Chen

Jing Liu

Yu-Jun Wang

Kuan Ning

Jing-Gen Liu

Zhi-Qiang Liu

Affiliations

Soon will be listed here.

Abstract

Glutamatergic neurons in ventral pallidum (VP) were recently reported to mediate motivational and emotional behavior, but its role in opioid addiction still remains to be elucidated. In this study we investigated the function of VP in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm. By use of cell-type-specific fiber photometry, we showed that the calcium activity of VP were inhibited during heroin self-administration and context-induced relapse, but activated after extinction in a new context. The drug seeking behavior was accompanied by the decreased calcium signal of VP. Chemogenetic manipulation of VP bidirectionally regulated heroin taking and seeking behavior. Anterograde tracing showed that the lateral habenula, one of the epithalamic structures, was the major output region of VP, and its neuronal activity was consistent with VP in different phases of heroin addiction and contributed to the motivation for heroin. VP axon terminals in LHb exhibited dynamic activity in different phases of heroin addiction. Activation of VP-LHb circuit reduced heroin seeking behavior during context-induced relapse. Furthermore, the balance of excitation/inhibition from VP to LHb was shifted to enhanced glutamate transmission after extinction of heroin seeking motivation. Overall, the present study demonstrated that the activity of VP was involved in the regulation of heroin addiction and identified the VP-LHb pathway as a potential intervention to reduce heroin seeking motivation.

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