Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA

Wei, Chao; Han, Xiao; Weng, Danwei; Feng, Qiru; Qi, Xiangbing; Li, Jin; Luo, Minmin

doi:10.1038/s41421-018-0060-z

Cited by 64 publications

(47 citation statements)

References 70 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, some opioids produce dramatic increases in dopamine, whereas others have very little effect (Gottås et al, 2014;Vander Weele et al, 2014). Furthermore, electrophysiological experiments have shown that neurons in the striatum respond in a very different manner to heroin versus cocaine self-administration (Chang et al, 1998;Wei et al, 2018), suggesting that the effects of the two drugs are encoded differently in this brain area.…”

Section: Introductionmentioning

confidence: 99%

Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH

Vassilev

Avvisati

Koya

et al. 2020

eNeuro

View full text Add to dashboard Cite

Despite the still prevailing notion of a shared substrate of action for all addictive drugs, there is evidence suggesting that opioid and psychostimulant drugs differ substantially in terms of their neurobiological and behavioral effects. These differences may reflect separate neural circuits engaged by the two drugs. Here we used the catFISH (cellular compartment analysis of temporal activity by fluorescence in situ hybridization) technique to investigate the degree of overlap between neurons engaged by heroin versus cocaine in adult male Sprague Dawley rats. The catFISH technique is a within-subject procedure that takes advantage of the different transcriptional time course of the immediate-early genes homer 1a and arc to determine to what extent two stimuli separated by an interval of 25 min engage the same neuronal population. We found that throughout the striatal complex the neuronal populations activated by noncontingent intravenous injections of cocaine (800 g/kg) and heroin (100 and 200 g/kg), administered at an interval of 25 min from each other, overlapped to a much lesser extent than in the case of two injections of cocaine (800 g/kg), also 25 min apart. The greatest reduction in overlap between populations activated by cocaine and heroin was in the dorsomedial and dorsolateral striatum (ϳ30% and ϳ22%, respectively, of the overlap observed for the sequence cocaine-cocaine). Our results point toward a significant separation between neuronal populations activated by heroin and cocaine in the striatal complex. We propose that our findings are a proof of concept that these two drugs are encoded differently in a brain area believed to be a common neurobiological substrate to drug abuse.

show abstract

Section: Introductionmentioning

confidence: 99%

Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH

Vassilev

Avvisati

Koya

et al. 2020

eNeuro

View full text Add to dashboard Cite

show abstract

“…To demonstrate that FLiCRE can detect elevated neural activity in vivo , we injected AAVs encoding FLiCRE and TRE-mCherry in the ventral tegmental area (VTA) of wildtype mice and implanted an optical fiber above the VTA to deliver blue light. To elevate calcium levels in the VTA, we injected mice with nicotine intraperitoneally (Wei et al, 2018) and delivered blue light to the VTA for 15 min. ~18 hrs later we analyzed the TRE-mCherry expression ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

A molecular calcium integrator reveals a striatal cell-type driving aversion

Kim

Sánchez

Hoerbelt

et al. 2020

Preprint

View full text Add to dashboard Cite

The ability to record transient cellular events in the DNA or RNA of cells would enable precise, large-scale analysis, selection, and reprogramming of heterogeneous cell populations. Here we report a molecular technology for stable genetic tagging of cells that exhibit activity-related increases in intracellular calcium concentration (FLiCRE). We used FLiCRE to transcriptionally label activated neural ensembles in the nucleus accumbens of the mouse brain during brief stimulation of aversive inputs. Using single-cell RNA sequencing, we detected FLiCRE transcripts among the endogenous transcriptome, providing simultaneous readout of both cell-type and calcium activation history. We identified a cell-type in the nucleus accumbens activated downstream of long-range excitatory projections. Taking advantage of FLiCRE′s modular design, we expressed an optogenetic channel selectively in this cell-type, and showed that direct recruitment of this otherwise genetically-inaccessible population elicits behavioral aversion. The specificity and minute-resolution of FLiCRE enables molecularly-informed characterization, manipulation, and reprogramming of activated cellular ensembles.

show abstract

“…Cocaine blocks dopamine reuptake in synapses, and dopamine accumulated in the synapse increases the activity of inhibitory neurons from the NAc, resulting in reduction of brain activity 53 . On the other hand, heroin suppresses inhibitory neurons projecting to the ventral tegmental area (VTA), resulting in augmentation of VTA activity and dopamine release 54 . Therefore, as cocaine and heroin differently affect the transmission of neurotransmitters including dopamine, it is believed that expression of chemical synaptic transmission‐related genes may also be different between the two drugs.…”

Section: Discussionmentioning

confidence: 99%

Gene expression in the striatum of cynomolgus monkeys after chronic administration of cocaine and heroin

Choi

Jin

Kim

et al. 2021

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Cocaine and heroin cause impairment of neural plasticity in the brain including striatum. This study aimed to identify genes differentially expressed in the striatum of cynomolgus monkeys in response to cocaine and heroin. After chronic administration of cocaine and heroin in the monkeys, we performed large‐scale transcriptome profiling in the striatum using RNA‐Seq technology and analysed functional annotation. We found that 547 and 1238 transcripts were more than 1.5‐fold up‐ or down‐regulated in cocaine‐ and heroin‐treated groups, respectively, compared to the control group, and 3432 transcripts exhibited differential expression between cocaine‐ and heroin‐treated groups. Functional annotation analysis indicated that genes associated with nervous system development (NAGLU, MOBP and TTL7) and stress granule disassembly (KIF5B and KLC1) were differentially expressed in the cocaine‐treated group compared to the control group, whereas gene associated with neuron apoptotic process (ERBB3) was differentially expressed in the heroin‐treated group. In addition, IPA network analysis indicated that genes (TRAF6 and TRAF3IP2) associated with inflammation were increased by the chronic administration of cocaine and heroin. These results provide insight into the correlated molecular mechanisms as well as the upregulation and down‐regulation of genes in the striatum after chronic exposure to cocaine and heroin.

show abstract

Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA

Cited by 64 publications

References 70 publications

Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH

Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH

A molecular calcium integrator reveals a striatal cell-type driving aversion

Gene expression in the striatum of cynomolgus monkeys after chronic administration of cocaine and heroin

Contact Info

Product

Resources

About