scholarly journals ΔFosB: A Molecular Mechanism of MDMA Dependence

2021 ◽  
Author(s):  
◽  
Jason Foote
Keyword(s):  
The Other ◽  
Infralimbic Cortex ◽  
Self Administration ◽  
Brain Areas ◽  
Caudate Putamen ◽  
Future Studies ◽  
Active Lever ◽  
Transcriptional Changes ◽  
Administration Methods

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) is a widely used illicit substance and some users show signs of abuse and dependence. It has been suggested that addiction reflects persistent neuroplasticity and one proposed mechanism has been a change in the expression of the transcription factor, ΔFosB.  Objectives. This study determined whether ΔFosB expression in reward-relevant brain areas was altered as a function of MDMA self-administration.  Methods. Rats were separated into triads. One rat self-administered MDMA (master rat) and the other 2 rats received either MDMA (yoked MDMA) or saline (yoked saline) infusions contingent on the behaviour of the master rat. Testing continued until a total intake of 350 mg/kg of MDMA was delivered. Two days following the final self-administration session, rats were sacrificed and perfused transcardially. Brains were removed, and ΔFosB immunohistochemistry was conducted. ΔFosB expression in striatum and medial prefrontal cortex was compared across groups.  Results. Unfortunately the tissue from many of the yoked MDMA rats was compromised and therefore data from this group were not included in any analyses. MDMA self-administration produced a significantly greater expression of ΔFosB in the ventromedial and ventrolateral portions of the caudate putamen when compared to expression produced following yoked saline exposure. Within the infralimbic cortex, accumbens shell and dorsolateral caudate putamen differences approached significance. A significant correlation between ΔFosB expression in the ventromedial caudate putamen and cumulative active lever presses across the final 5 days of self-administration was also found.  Conclusions. These findings provide the first evidence of MDMA-induced expression of ΔFosB. Increased expression of ΔFosB was observed in regions associated with the development and maintenance of drug addiction. These data support the idea that induction of ΔFosB may present a mechanism by which MDMA can induce alterations in genetic transcription, which may underlie the development of MDMA dependence.  Future studies should utilise antagonism of ΔFosB via region-selective administration of Δc-jun in order to further elucidate the role of these transcriptional changes in the development and maintenance of self-administration.</p>

scholarly journals ΔFosB: A Molecular Mechanism of MDMA Dependence

2021 ◽  
Author(s):  
◽  
Jason Foote
Keyword(s):  
The Other ◽  
Infralimbic Cortex ◽  
Self Administration ◽  
Brain Areas ◽  
Caudate Putamen ◽  
Future Studies ◽  
Active Lever ◽  
Transcriptional Changes ◽  
Administration Methods

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) is a widely used illicit substance and some users show signs of abuse and dependence. It has been suggested that addiction reflects persistent neuroplasticity and one proposed mechanism has been a change in the expression of the transcription factor, ΔFosB.  Objectives. This study determined whether ΔFosB expression in reward-relevant brain areas was altered as a function of MDMA self-administration.  Methods. Rats were separated into triads. One rat self-administered MDMA (master rat) and the other 2 rats received either MDMA (yoked MDMA) or saline (yoked saline) infusions contingent on the behaviour of the master rat. Testing continued until a total intake of 350 mg/kg of MDMA was delivered. Two days following the final self-administration session, rats were sacrificed and perfused transcardially. Brains were removed, and ΔFosB immunohistochemistry was conducted. ΔFosB expression in striatum and medial prefrontal cortex was compared across groups.  Results. Unfortunately the tissue from many of the yoked MDMA rats was compromised and therefore data from this group were not included in any analyses. MDMA self-administration produced a significantly greater expression of ΔFosB in the ventromedial and ventrolateral portions of the caudate putamen when compared to expression produced following yoked saline exposure. Within the infralimbic cortex, accumbens shell and dorsolateral caudate putamen differences approached significance. A significant correlation between ΔFosB expression in the ventromedial caudate putamen and cumulative active lever presses across the final 5 days of self-administration was also found.  Conclusions. These findings provide the first evidence of MDMA-induced expression of ΔFosB. Increased expression of ΔFosB was observed in regions associated with the development and maintenance of drug addiction. These data support the idea that induction of ΔFosB may present a mechanism by which MDMA can induce alterations in genetic transcription, which may underlie the development of MDMA dependence.  Future studies should utilise antagonism of ΔFosB via region-selective administration of Δc-jun in order to further elucidate the role of these transcriptional changes in the development and maintenance of self-administration.</p>

scholarly journals A Focus on the Functions of Area 25

2019 ◽  
Vol 9 (6) ◽  
pp. 129 ◽  
Author(s):  
Laith Alexander ◽  
Hannah Clarke ◽  
Angela Roberts
Keyword(s):  
Negative Affect ◽  
Affective Disorders ◽  
Anterior Cingulate ◽  
Emotional States ◽  
Infralimbic Cortex ◽  
Future Studies ◽  
Mood Changes ◽  
Behavioral Evidence ◽  
Putative Homologue

Subcallosal area 25 is one of the least understood regions of the anterior cingulate cortex, but activity in this area is emerging as a crucial correlate of mood and affective disorder symptomatology. The cortical and subcortical connectivity of area 25 suggests it may act as an interface between the bioregulatory and emotional states that are aberrant in disorders such as depression. However, evidence for such a role is limited because of uncertainty over the functional homologue of area 25 in rodents, which hinders cross-species translation. This emphasizes the need for causal manipulations in monkeys in which area 25, and the prefrontal and cingulate regions in which it is embedded, resemble those of humans more than rodents. In this review, we consider physiological and behavioral evidence from non-pathological and pathological studies in humans and from manipulations of area 25 in monkeys and its putative homologue, the infralimbic cortex (IL), in rodents. We highlight the similarities between area 25 function in monkeys and IL function in rodents with respect to the regulation of reward-driven responses, but also the apparent inconsistencies in the regulation of threat responses, not only between the rodent and monkey literatures, but also within the rodent literature. Overall, we provide evidence for a causal role of area 25 in both the enhanced negative affect and decreased positive affect that is characteristic of affective disorders, and the cardiovascular and endocrine perturbations that accompany these mood changes. We end with a brief consideration of how future studies should be tailored to best translate these findings into the clinic.

The sugar intake of businessmen and its inverse relationship with relative weight

1972 ◽  
Vol 27 (3) ◽  
pp. 449-460 ◽  
Author(s):  
J. F. Richardson
Keyword(s):  
Inverse Relationship ◽  
Direct Relationship ◽  
Relative Weight ◽  
Positive Association ◽  
Sugar Consumption ◽  
Self Administration ◽  
Future Studies ◽  
Actual Weight ◽  
Sugar Intake

1. Yudkin's (1967) questionnaire on the dietary intake of sugar was given to 415 businessmen for self-administration.1. The results showed an inverse relationship between sugar intake and relative weight (actual weight as a percentage of expected weight for height and age) and additional evidence suggests a direct relationship between sugar intake and adequate exercise.2. The statement that ‘sugar was restricted’ was shown to be a factor of considerable importance affecting the reported level of sugar intake and should be taken into account when comparing different series.3. The positive association between cigarette smoking and mean sugar consumption in this series was due to the low-sugar intake of ex-smokers.4. In future studies on the role of sucrose in the aetiology of ischaemic disease, both smoking habits and levels of activity should be recorded.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

Surrogate role of kinetic of perioperative circulating cancer cells (CTCs) in patients with liver metastases (M) of colorectal cancer (CRC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Lucia Teijeira ◽  
Antonio Viudez ◽  
Maria L Antelo ◽  
Antonio Tarifa ◽  
Cruz Zazpe ◽  
...  
Keyword(s):  
Pathological Response ◽  
The Other ◽  
Kinetic Behavior ◽  
Wild Type ◽  
Cellsearch System ◽  
Future Studies ◽  
Circulating Cancer Cells ◽  
Kras Status

e21086 Background: Kinetic behavior of perioperative CTCs in pts with liver CRC M has been little explored. The aim of this study was to quantified CTCs performance before/just performed and 3 months after radical liver surgery (LS) in pts with CRC M and analyzed the surrogate role of CTCs determinations in DFS and OS. Methods: 7.5 ml of blood were drawn in CellSave tubes. CTCs were isolated and enumerated before/just perfomed and 3 months after radical LS. CTCs were immunomagnetically separated and fluorescently labeled using the CellSearch System (Veridex®/Immunicon Corp.) Results: From February 2009 to December 2011, 35 pts were included. Median age was 61 (45-77); 53.7 % men. Kras status: 66.7% wild-type and 33.3% mutated; 48.6% with synchronous disease. Fong-Criteria (FC) distribution: 31.4% pts with 1 FC, 37.1% pts with 2 FC and 31.4% pts with 3 FC, of whom 60% received neoadjuvant (90% fluoropirimidines-based; 33.3% cetuximab-based; 38% bevacizumab-based) and 77.1% adjuvant treatment. PR and SD were observed in 60% and 40% of pts, respectively. In 70.7% of cases, limited LS were done (68.3% R0, median metastases resected:3) Of the 17 pts analysed, pCR were observed in 2 (12%) with 7 other pts (41%) with major pathological response. With a median of follow-up of 20 months (media 21.3; 95% CI:17.3-41.4) progression disease occurred in 13 pts (55.6% with liver progression), and 5 pts died. Median CTCs was 1 before (0-2: 76%; ≥3: 24%) and just performed surgery (0-2: 65%; ³3: 35%) and 0 in the 3 months determination (0-2: 94.1%; ³3: 5.9%). In the presurgery analysis, DFS was 15 months for the CTCs ≥3 group and 33 months for <3 CTCs (HR: 0.95; 95% CI:0.34-2.64) while in the postsurgery analysis, DFS was 13 months in CTCs ≥3 group and 33 months for <3 CTCs (HR: 1.11; 95% CI:0.37-3.29) CTCs ≥3 group after surgery, OS was 33 months, not having reached in the other groups. Conclusions: There is a marked difference in DFS in favor of pts with CTCs levels 0-2 before and just performed surgery. Our study shows a slight increase in CTCs quantification after LS, instead a significant CTCs decrease was observed after adjuvant therapy. Role of radical LS in kinetic of CTCs should continue to be analysed in future studies.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

scholarly journals Dissociation between Private and Social Counterfactual Value Signals Following Ventromedial Prefrontal Cortex Damage

2019 ◽  
Vol 31 (5) ◽  
pp. 639-656 ◽  
Author(s):  
Nadège Bault ◽  
Giuseppe di Pellegrino ◽  
Martina Puppi ◽  
Gaëlle Opolczynski ◽  
Alessia Monti ◽  
...  
Keyword(s):  
Decision Making ◽  
Prefrontal Cortex ◽  
Ventromedial Prefrontal Cortex ◽  
The Other ◽  
Healthy Controls ◽  
Risky Decision ◽  
Brain Areas ◽  
Social Settings ◽  
Neuropsychological Study

Individuals learn by comparing the outcome of chosen and unchosen actions. A negative counterfactual value signal is generated when this comparison is unfavorable. This can happen in private as well as in social settings—where the foregone outcome results from the choice of another person. We hypothesized that, despite sharing similar features such as supporting learning, these two counterfactual signals might implicate distinct brain networks. We conducted a neuropsychological study on the role of private and social counterfactual value signals in risky decision-making. Patients with lesions in the ventromedial prefrontal cortex (vmPFC), lesion controls, and healthy controls repeatedly chose between lotteries. In private trials, participants could observe the outcomes of their choices and the outcomes of the unselected lotteries. In social trials, participants could also see the other player's choices and outcome. At the time of outcome, vmPFC patients were insensitive to private counterfactual value signals, whereas their responses to social comparison were similar to those of control participants. At the time of choice, intact vmPFC was necessary to integrate counterfactual signals in decisions, although amelioration was observed during the course of the task, possibly driven by social trials. We conclude that if the vmPFC is critical in processing private counterfactual signals and in integrating those signals in decision-making, then distinct brain areas might support the processing of social counterfactual signals.

scholarly journals Central role of somatosensory processes in sexual arousal as identified by neuroimaging techniques

2007 ◽  
Vol 30 (2) ◽  
pp. 217-217 ◽  
Author(s):  
Harold Mouras
Keyword(s):  
Sexual Arousal ◽  
Penile Erection ◽  
Neural Correlates ◽  
The Other ◽  
Affective Neuroscience ◽  
Brain Areas ◽  
New Approach ◽  
The One ◽  
Neuroimaging Techniques

AbstractResearch on the neural correlates of sexual arousal is a growing field of research in affective neuroscience. A new approach studying the correlation between the hemodynamic cerebral response and autonomic genital response has enabled distinct brain areas to be identified according to their role in inducing penile erection, on the one hand, and in representing penile sensation, on the other.

scholarly journals The Role of NMDA receptors in rat propofol self-administration

2020 ◽  
Author(s):  
Bei ping Chen ◽  
Xi-xi Huang ◽  
Dong-mei Dong ◽  
Hui Wu ◽  
Tian-qi Zhu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Neural Plasticity ◽  
Fixed Ratio ◽  
Study Groups ◽  
Ratio Schedule ◽  
Self Administration ◽  
Mk 801 ◽  
Anesthetic Agents ◽  
Administration Methods

Abstract Aim Propofol is among the most frequently used anesthetic agents, and it has the potential for abuse. The N-methyl-D-aspartate (NMDA) receptors are key mediators of both neural plasticity and development, as well as of addiction and neurodegeneration. Herein we explored the role of these receptors in rat propofol self-administration. Methods Rats were trained to self-administer propofol (1.7 mg/kg/infusion) using an FR fixed ratio schedule of the course of 14 sessions (3 h/day). After training, rats were intraperitoneally administered the non-competitive NDMA receptor antagonist MK-801, and then 10 minutes later were subjected to a propofol self-administration session. Results: After training, rats had acquired the ability to self-administer propofol successfully, as evidenced by a significant and stable rise in active nose-pokes leading to propofol administration relative to control nose-pokes (P<0.01) and became stable. Relative to control rats, rats that had been injected with 0.2 mg/kg MK-801 exhibited significantly more propofol infusions (F(3, 28)=4.372, P<0.01), whereas infusions were comparable in the groups administered 0.1 mg/kg and 0.4 mg/kg. In addition, MK-801 failed to alter numbers of active (F(3, 28)=1.353, P>0.05) or inactive (F(3, 28)=0.047, P>0.05) responses in study groups. Animals administered 0.4 mg/kg MK-801 exhibited significantly fewer infusions than animals administered 0.2 mg/kg (P=0.006, P<0.01). In contrast, however, animals in the 0.4 mg/kg MK-801 group exhibited a significant reduction in the number of active nose poke responses (F(3, 20)=20.8673, P<0.01) and the number of sucrose pellets (F(3, 20)=23.77, P<0.01), with increased locomotor activity (F(3, 20)=22.812, P<0.01). Conclusion These findings indicate that NMDA receptors may play a role in regulating rat self-administration of propofol.

scholarly journals Handling Innovation in Small Family Firms: The Role of Context

2020 ◽  
Vol 15 (5) ◽  
pp. 60
Author(s):  
Michela Floris ◽  
Angela Dettori ◽  
Cinzia Dessi
Keyword(s):  
Family Firms ◽  
Innovation Management ◽  
The Other ◽  
Future Studies ◽  
Small Family ◽  
Local Contexts ◽  
Constant Tension ◽  
The One ◽  
Practical Implications

Innovation management in family firms is a paradoxical challenge. The constant tension between innovation and tradition confers to this topic a fascinating mystery area that calls to action scholarly efforts and further studies to underscore whether family firms are innovating or not. This debate becomes even more intriguing and interesting when family businesses are small-sized and embedded in local contexts strongly attached to traditions and cultures that inhibit change. Based on the curiosity of analyzing the innovation proclivity of small family firms rooted in such a context and building on previous studies that were focused on innovation in family run businesses, we deeply investigated two cases. Findings uncovered a twofold and opposite role of the context:&nbsp; on the one hand, a constraint and, on the other hand, leverage of innovation. Interesting scholars and practical implications are discussed, and future studies are suggested.

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