Electro‐acupuncture alleviates adolescent cocaine exposure‐enhanced anxiety‐like behaviors in adult mice by attenuating the activities of PV interneurons in PrL

Abstract

We recently found that adolescent cocaine exposure (ACE) resulted in an enhancement of the γ‐aminobutyric acid (GABA) neurotransmitter system in the prelimbic cortex (PrL) of adult mice. Here, we aim to further investigate the role of GABAergic transmission, especially parvalbumin (PV) interneurons within PrL in the development of ACE‐induced anxiety‐like behavior, and to assess whether and how electro‐acupuncture (EA) therapeutically manage the ACE‐induced abnormal behaviors in adulthood. ACE mice exhibited the enhanced anxiety‐like behaviors in their adulthood, accompanied by increased GABAergic transmission and PV interneurons in PrL. Chemogenetic blocking PV interneurons in PrL alleviated ACE‐enhanced anxiety‐like behaviors in mice. Importantly, 37‐day EA treatments (mixture of 2 Hz/100 Hz, 1 mA, 30 minutes once a day) at the acupoints of Yintang (GV29) and Baihui (GV20) also alleviated ACE‐induced anxiety‐like behaviors, and rescued ACE‐impaired GABAergic neurotransmitter system and PV interneurons in PrL. In parallel, EA treatments further suppressed the activities of pyramidal neurons in PrL, suggesting that EA treatments seem to perform it beneficial effects on the ACE‐induced abnormal emotional behaviors by “calming down” the whole PrL. Collectively, these findings revealed that hyper‐function of GABAergic transmission, especially mediating by PV interneurons in PrL may be key etiology underlying ACE‐induced anxiety‐like behaviors. At least by normalizing the function of GABAergic and PV interneurons, EA may represent a promising therapeutic strategy for managing adolescent substance use‐related emotional disorders.

Dopamine receptor 1 on CaMKII-positive neurons within claustrum mediates adolescent cocaine exposure-induced anxiety-like behaviors and electro-acupuncture therapy

“…Consistent with our previous finding (18), we found that ACE mice exhibited obvious anxiety-like behaviors in their adulthood, which was efficiently suppressed by electro-acupuncture (EA) at acupoints of Baihui (GV 20 Drug abuse such as cocaine during adolescence, a sensitive period of heightened propensity to substance use in humans, enhance risk of developing psychiatric disorders, which even persist into adulthood (2,10,28). Consistent with human and animal studies on ACE (9,18,29,30), ACE mice exhibited more anxiety in their adulthood here. Moreover, we found that CaMKII CL activity was involved in the process of anxiety in ACE mice.…”

“…The electro-acupuncture (EA), a kind of peripheral acupuncture with electric stimulation, has been shown to improve anxiety without adverse effects (16,17). Previously, we found that EA at acupoints of Baihui (GV 20) and Yintang (GV 29) during withdrawal period effectively reduced anxiety in ACE mice of adulthood (18). The claustrum (CL) is a thin stripped nucleus situated between the insular cortex and striatum, which is composed by 90 percent of CaMKIIpositive glutamatergic neurons (CaMKII CL ) (19,20).…”

Complementary and Alternative Medicine for Substance Use Disorders: A Scientometric Analysis and Visualization of Its Use Between 2001 and 2020

“…Evidence from experiments and clinics has confirmed that it has an improved effect on SUDs (49,50). Recent studies have proven that EA could alleviate substance abuse, inducing anxiety-like behaviors, in people and mice (22,51).…”

“…Complementary therapy for SUDs, especially acupuncture, is not widely used, regardless of its efficiency. Moreover, the involvement of adolescents in CAM for SUDs is considered distressing (21)(22)(23).…”

The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder

“…Interestingly, a large number of studies reported that EA exerts neuroprotective effects by regulating the structure and function of the hippocampus and PFC (He et al, 2018;Chen et al, 2019;Marcus et al, 2020). For example, preclinical studies reported that EA ameliorate learning, memory and emotion regulating ability via regulating the neurochemical metabolism, cannabinoid receptors expression as well as activation of PV interneurons in the hippocampus and PFC (He et al, 2018;Chen et al, 2019;Marcus et al, 2020;Nie et al, 2020), which are regions of central importance in PTSD due to their prominent role in the neuroendocrine stress response and memory Lambert and McLaughlin, 2019;Smith et al, 2019). Clinical and preclinical studies have previously reported that EA is protective against PTSD (Wang et al, 2012;Li et al, 2020).…”