Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction

The Phosphodiesterase-4 Inhibitor Rolipram Attenuates Heroin-Seeking Behavior Induced By Cues Or Heroin Priming In Rats

Inhibition of phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP) increases intracellular cAMP/cAMP-response element binding protein (CREB) signaling. Activation of this signaling is considered as an important compensatory response that decreases motivational properties of drugs of abuse. However, it is not known whether PDE4 is involved in heroin seeking. Self-administration of heroin (5

Polypyrimidine tract binding protein knockdown reverses depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons

Background and objectivesDepression is a common comorbidity of dementia and may be a risk factor for dementia. Accumulating evidence has suggested that the cholinergic system plays a central role in dementia and depression, and the loss of cholinergic neurons is associated with memory decline in aging and Alzheimer’s patients. A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) is correlated with depression and dysfunction of cognition in mice. In this study, we examined the potential regenerative mechanisms of knockdown the RNA-binding protein polypyrimidine tract binding protein (PTB) in reversing depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons.MethodsWe lesioned cholinergic neurons in mice induced by injection of 192 IgG-saporin into HDB; then, we injected either antisense oligonucleotides or adeno-associated virus-shRNA (GFAP promoter) into the injured area of HDB to deplete PTB followed by a broad range of methodologies including behavioral examinations, Western blot, RT-qPCR and immunofluorescence.ResultsWe found that the conversion of astrocytes to newborn neurons by using antisense oligonucleotides on PTB in vitro, and depletion of PTB using either antisense oligonucleotides or adeno-associated virus-shRNA into the injured area of HDB could specifically transform astrocytes into cholinergic neurons. Meanwhile, knockdown of PTB by both approaches could relieve the depression-like behaviors shown by sucrose preference, forced swimming or tail-suspension tests, and alleviate cognitive impairment such as fear conditioning and novel object recognition in mice with lesioned cholinergic neurons.ConclusionThese findings suggest that supplementing cholinergic neurons after PTB knockdown may be a promising therapeutic strategy to revert depression-like behaviors and cognitive impairment

Circulating plasma and exosome levels of the miR-320 family as a non-invasive biomarker for methamphetamine use disorder

The neurobiological mechanism underlying methamphetamine (MA) use disorder was still unclear, and no specific biomarker exists for clinical diagnosis of this disorder. Recent studies have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MA addiction. The purpose of this study was to identify novel miRNAs for the diagnosis biomarkers of MA user disorder. First, members of the miR-320 family, including miR-320a-3p, miR-320b, and miR-320c, were screened and analyzed in the circulating plasma and exosomes by microarray and sequencing. Secondly, plasma miR-320 was quantified by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in eighty-two MA patients and fifty age-gender-matched healthy controls. Meanwhile, we also analyzed exosomal miR-320 expression in thirty-nine MA patients and twenty-one age-matched healthy controls. Furthermore, the diagnostic power was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The expression of miR-320 significantly increased in plasma and exosomes of MA patients compared with healthy controls. The AUC of the ROC curves of miR-320 in plasma and exosomes of MA patients were 0.751 and 0.962, respectively. And the sensitivities of miR-320 were 0.900 and 0.846, respectively, whereas the specificities of miR-320 were 0.537 and 0.952, respectively, in plasma and exosomes in MA patients. And the increased plasma miR-320 was positively correlated with cigarette smoking, age of onset, and daily use of MA in MA patients. Finally, cardiovascular disease, synaptic plasticity, and neuroinflammation were predicted to be the target pathways related to miR-320. Taken together, our findings indicated that plasma and exosomal miR-320 might be used as a potential blood-based biomarker for diagnosing MA use disorder