Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression

Anderson, Sarah; Michaelides, Michael; Zarnegar, Parisa; Ren, Yanhua; Fagergren, Pernilla; Thanos, Panayotis K.; Wang, Gene Jack; Bannon, Michael J.; Neumaier, John F.; Keller, Éva; Volkow, Nora D.; Hurd, Yasmin L.

doi:10.1172/jci70395

Cited by 45 publications

(43 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[16][17][18] Moreover, reduced PDYN expression in the human brain is associated with opiate dependency. 35,36 Interestingly, in the present study the continuous exposure condition of ELF-EMF was associated with the lower expression levels of the PDYN. It may indicate that in cells exposed to ELF-EMF the PDYN expression level significantly decreased via production of ROS.…”

Section: Discussionsupporting

confidence: 45%

Expression levels of PDYN and OPRM1 genes in SH-SY5Y cells exposed to 50 Hz electromagnetic field

Mahmoudinasab¹,

Saadat²

2018

Pol Ann Med

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 45%

Expression levels of PDYN and OPRM1 genes in SH-SY5Y cells exposed to 50 Hz electromagnetic field

Mahmoudinasab¹,

Saadat²

2018

Pol Ann Med

View full text Add to dashboard Cite

show abstract

“…Two Herpes Simplex Virus (HSV) vectors were constructed for the purposes of these studies based on vectors that we and others have extensively characterized with regard to their time course and selectivity of expression (Ferguson et al, 2011, Anderson et al, 2013, Ferguson et al, 2013, Michaelides et al, 2013). HSV is an enveloped, double-stranded DNA virus that selectively enters neurons via glycoprotein interactions.…”

Section: Methodsmentioning

confidence: 99%

“…the strain is not substantially retrogradely transported) (Fink et al, 1996). The first utilizes preprodynorphin promoter (pDYN) to drive transgene expression in dMSNs while the second uses the preproenkephalin promoter (pENK) to target iMSNs; both are >90% selective (Ferguson et al, 2011, Anderson et al, 2013, Ferguson et al, 2013, Michaelides et al, 2013). To allow us to distinguish from endogenous 5-HT 6 receptors, a double hemagglutinin (2xHA) epitope-tag was introduced to the N terminal of the rat 5-HT 6 receptor gene by cloning an oligonucleotide in-frame upstream of the 5-HT 6 sequence using pBlueScript as this does not interfere with receptor functionality as shown previously (Mitchell et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

“…These studies support the view of dMSNs and iMSNs as generally activating and inhibiting behavioral output, respectively. For the purposes of this study, we developed viral vectors that utilize the preprodynorphin or preproenkephalin promoters to manipulate rat dMSNs and iMSNs selectively, based on known well-characterized viral vector promotors (Ferguson et al, 2011, Anderson et al, 2013, Ferguson et al, 2013, Michaelides et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deconstructing 5-HT6 receptor effects on striatal circuit function

2015

View full text Add to dashboard Cite

Medium spiny neurons (MSNs) constitute 95% of neurons in dorsal striatum subdivided into direct (striatonigral) and indirect (striatopallidal) pathways. Whereas D1 and D2 receptors and several neuropeptides, including dynorphin and enkephalin, are differentially expressed in these neurons, 5-HT6 receptors are expressed in both pathways. Previous results demonstrate that concurrent 5-HT6 receptor overexpression in MSNs of both pathways in dorsomedial striatum interferes with instrumental learning and that 5-HT6 overexpression in dorsolateral striatum relieves rats from inflexible habitual behaviors. We hypothesized that 5-HT6 receptor-mediated co-activation of both pathways interferes with the differential activation/inhibition of direct/indirect pathways by dopamine. To test this idea, we cloned novel viral vectors to selectively overexpress 5-HT6 receptors in direct or indirect pathway MSNs to deconstruct their role in modulating instrumental learning and habitual responding. We found that increasing 5-HT6 receptor expression in either direct or indirect pathway MSNs of the posterior dorsomedial striatum selectively enhanced or impaired initial acquisition of a discrete instrumental learning task, respectively, though all rats were ultimately able to learn the task. In a separate set of experiments, 5-HT6 receptor overexpression in indirect pathway MSNs of the dorsolateral striatum facilitated behavioral flexibility in rats overtrained on a repetitive pressing task using a variable interval schedule of reinforcement, during an omission contingency training session and subsequent probe testing. Together these findings further the notion that 5-HT6 signaling causes balanced activation of opposing MSN pathways by serotonin in sub-regions of dorsal striatum allowing for more reflective modalities of behavior.

show abstract

“…Anderson et al (Anderson et al, 2013) employed DREADDs in a novel way, which they termed DREADD-assisted metabolic mapping (DREAMM; see also (Michaelides et al, 2013)), to interrogate wider circuit activity after hM4Di DREADD inhibition of dynorphin-expressing neurons in rat periamygdaloid cortex (PAC). They found that dynorphin mRNA in PAC is higher in humans and rats with heroin self-administration history, so they measured effects of DREADD-mediated inhibition of PAC dynorphin neurons on behavior, and on wider brain activity as measured by radiolabeled glucose utilization with PET imaging.…”

Section: Section 2 – Highlights Of Dreadd Applications In Behavioral mentioning

confidence: 99%

DREADDS: Use and application in behavioral neuroscience.

Smith¹,

Bucci²,

Luikart³

et al. 2016

Behavioral Neuroscience

213

155

View full text Add to dashboard Cite

Technological advances over the last decade are changing the face of behavioral neuroscience research. Here we review recent work on the use of one such transformative tool, chemogenetics (or Designer Receptors Exclusively Activated by Designer Drugs, DREADDS), in behavioral neuroscience research. As transformative technologies such as DREADDs are introduced, applied, and refined, their utility in addressing complex questions on behavior and cognition become clear and exciting. In the behavioral neuroscience field, remarkable new findings now regularly appear as a result of the ability to monitor and intervene in neural processes with high anatomical precision as animals behave in complex task environments. As these new tools are applied to behavioral questions, individualized procedures for their use find their way into diverse labs. Thus, “tips of the trade” become important for wide dissemination not only for laboratories that are using the tools but also those that are interested in incorporating them into their own work. Our aim is to provide an up-to-date perspective on how the DREADD technique is being used for research on learning and memory, decision making, and goal-directed behavior, as well as to provide suggestions and considerations for current and future users based on our collective experience.

show abstract

Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression

Cited by 45 publications

References 55 publications

Expression levels of PDYN and OPRM1 genes in SH-SY5Y cells exposed to 50 Hz electromagnetic field

Expression levels of PDYN and OPRM1 genes in SH-SY5Y cells exposed to 50 Hz electromagnetic field

Deconstructing 5-HT6 receptor effects on striatal circuit function

DREADDS: Use and application in behavioral neuroscience.

Contact Info

Product

Resources

About