infralimbic cortex
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2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mayumi Watanabe ◽  
Akira Uematsu ◽  
Joshua P. Johansen

AbstractThe ability to extinguish aversive memories when they are no longer associated with danger is critical for balancing survival with competing adaptive demands. Previous studies demonstrated that the infralimbic cortex (IL) is essential for extinction of learned fear, while neural activity in the prelimbic cortex (PL) facilitates fear responding and is negatively correlated with the strength of extinction memories. Though these adjacent regions in the prefrontal cortex maintain mutual synaptic connectivity, it has been unclear whether PL and IL interact functionally with each other during fear extinction learning. Here we addressed this question by recording local field potentials (LFPs) simultaneously from PL and IL of awake behaving rats during extinction of auditory fear memories. We found that LFP power in the fast gamma frequency (100–200 Hz) in both PL and IL regions increased during extinction learning. In addition, coherency analysis showed that synchronization between PL and IL in the fast gamma frequency was enhanced over the course of extinction. These findings support the hypothesis that interregional interactions between PL and IL increase as animals extinguish aversive memories.


2021 ◽  
Vol 242 ◽  
pp. 113597
Author(s):  
Eden M. Anderson ◽  
Skyler Demis ◽  
Benjamin Wrucke ◽  
Annabel Engelhardt ◽  
Matthew C. Hearing

2021 ◽  
Author(s):  
◽  
Jason Foote

<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>


2021 ◽  
Author(s):  
◽  
Jason Foote

<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>


2021 ◽  
Author(s):  
◽  
Natasha Bukholt

<p>Background: MDMA preferentially releases serotonin (5HT) but following repeated exposure there is a decrease in this MDMA-produced effect. At the same time, some studies suggest an increase in MDMA-produced dopamine (DA) release following repeated exposure. The sensitised DA response is often accompanied by sensitisation of MDMA-produced locomotor activity. Because DAergic mechanisms have been implicated in the positively reinforcing properties of MDMA, these neuroadaptations might be relevant to MDMA self-administration.  Objectives: The main objective of this study was to determine whether MDMA self-administration and non-contingent MDMA exposure differentially affected the development of sensitisation to MDMA-produced hyperactivity. Additionally, the relationship between MDMA-produced hyperactivity and changes in c-fos expression in DA terminal regions was determined.  Methods: Triads of rats were designated ‘master’, ‘yoked MDMA’, or ‘yoked saline’. Lever press responding by the master rat resulted in an intravenous infusion of MDMA for both the master rat and the yoked MDMA rat, as well as an equal infusion of vehicle for the yoked control rat. Daily tests continued until a total of 350 mg/kg MDMA had been self-administered. Three days following the last self-administration session, forward and vertical locomotion produced by MDMA (5.0 mg/kg, i.p) were measured during a 2 hr test. Rats were sacrificed immediately following the behavioural test, and c-fos immunohistochemistry was measured.  Results: Repeated MDMA exposure resulted in sensitised forward and vertical locomotor activity. Sensitisation of the increase in forward locomotion was produced only in rats that self-administered MDMA; non-contingent MDMA administration failed to sensitise this behavioural response. In contrast, sensitisation to MDMA-produced vertical activity was produced following both contingent and non-contingent MDMA exposure. C-fos expression was reduced in ventrolateral, and ventromedial areas of the dorsal striatum, as well as the infralimbic cortex, after MDMA exposure, regardless of whether the exposure was via self-administration or yoked administration. A selective decrease in c-fos expression in the nucleus accumbens (NAc) core and the cingulate cortex was produced by MDMA self-administration. There was a negative correlation between MDMA-produced forward locomotor activity and MDMA-produced c-fos expression in the NAc core, cingulate cortex and infralimbic cortex. A negative correlation between rearing activity and MDMA-produced c-fos expression in the NAc core, NAc shell, cingulate cortex, and infralimbic cortex was also found.  Conclusions: These data provide evidence of behavioural sensitisation as a result of repeated MDMA exposure. Furthermore, MDMA-produced behavioural sensitisation was associated with a decrease in c-fos expression that was evident in the NAc and prefrontal cortex. Finally, region-specific changes in c-fos expression suggest an important role of neuroadaptations in the NAc core and the infralimbic cortex as a consequence of MDMA self-administration.</p>


2021 ◽  
Author(s):  
◽  
Natasha Bukholt

<p>Background: MDMA preferentially releases serotonin (5HT) but following repeated exposure there is a decrease in this MDMA-produced effect. At the same time, some studies suggest an increase in MDMA-produced dopamine (DA) release following repeated exposure. The sensitised DA response is often accompanied by sensitisation of MDMA-produced locomotor activity. Because DAergic mechanisms have been implicated in the positively reinforcing properties of MDMA, these neuroadaptations might be relevant to MDMA self-administration.  Objectives: The main objective of this study was to determine whether MDMA self-administration and non-contingent MDMA exposure differentially affected the development of sensitisation to MDMA-produced hyperactivity. Additionally, the relationship between MDMA-produced hyperactivity and changes in c-fos expression in DA terminal regions was determined.  Methods: Triads of rats were designated ‘master’, ‘yoked MDMA’, or ‘yoked saline’. Lever press responding by the master rat resulted in an intravenous infusion of MDMA for both the master rat and the yoked MDMA rat, as well as an equal infusion of vehicle for the yoked control rat. Daily tests continued until a total of 350 mg/kg MDMA had been self-administered. Three days following the last self-administration session, forward and vertical locomotion produced by MDMA (5.0 mg/kg, i.p) were measured during a 2 hr test. Rats were sacrificed immediately following the behavioural test, and c-fos immunohistochemistry was measured.  Results: Repeated MDMA exposure resulted in sensitised forward and vertical locomotor activity. Sensitisation of the increase in forward locomotion was produced only in rats that self-administered MDMA; non-contingent MDMA administration failed to sensitise this behavioural response. In contrast, sensitisation to MDMA-produced vertical activity was produced following both contingent and non-contingent MDMA exposure. C-fos expression was reduced in ventrolateral, and ventromedial areas of the dorsal striatum, as well as the infralimbic cortex, after MDMA exposure, regardless of whether the exposure was via self-administration or yoked administration. A selective decrease in c-fos expression in the nucleus accumbens (NAc) core and the cingulate cortex was produced by MDMA self-administration. There was a negative correlation between MDMA-produced forward locomotor activity and MDMA-produced c-fos expression in the NAc core, cingulate cortex and infralimbic cortex. A negative correlation between rearing activity and MDMA-produced c-fos expression in the NAc core, NAc shell, cingulate cortex, and infralimbic cortex was also found.  Conclusions: These data provide evidence of behavioural sensitisation as a result of repeated MDMA exposure. Furthermore, MDMA-produced behavioural sensitisation was associated with a decrease in c-fos expression that was evident in the NAc and prefrontal cortex. Finally, region-specific changes in c-fos expression suggest an important role of neuroadaptations in the NAc core and the infralimbic cortex as a consequence of MDMA self-administration.</p>


2021 ◽  
Author(s):  
Victória A. Müller Ewald ◽  
Jangjin Kim ◽  
Sean J. Farley ◽  
John H. Freeman ◽  
Ryan T. LaLumiere

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1632
Author(s):  
Gerard Batallé ◽  
Xue Bai ◽  
Enric Pouso-Vázquez ◽  
Gerad Roch ◽  
Laura Rodríguez ◽  
...  

Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H2S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H2S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H2S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system.


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