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Regulation of extinction-related plasticity by opioid receptors in the ventrolateral periaqueductal gray matter.

Parsons RG, Gafford GM, Helmstetter FJ - Front Behav Neurosci (2010)

Bottom Line: The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) in brain regions that likely participate in the consolidation of extinction learning.Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training.These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Wisconsin-Milwaukee Milwaukee, WI, USA.

ABSTRACT
Recent work has led to a better understanding of the neural mechanisms underlying the extinction of Pavlovian fear conditioning. Long-term synaptic changes in the medial prefrontal cortex (mPFC) are critical for extinction learning, but very little is currently known about how the mPFC and other brain areas interact during extinction. The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) in brain regions that likely participate in the consolidation of extinction learning. Inhibitors of opioid and N-methyl-d-aspartic acid (NMDA) receptors were applied to the ventrolateral periaqueductal gray matter (vlPAG) and amygdala shortly before extinction training. Results from these experiments show that blocking opioid receptors in the vlPAG prevented the formation of extinction memory, whereas NMDA receptor blockade had no effect. Conversely, blocking NMDA receptors in the amygdala disrupted the formation of fear extinction memory, but opioid receptor blockade in the same brain area did not. Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training. Only opioid receptor blockade in the vlPAG disrupted ERK phosphorylation in the mPFC and amygdala. These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

No MeSH data available.


Related in: MedlinePlus

Opioid receptor blockade does not affect ERK phosphorylation following four trials of extinction. (A) Schematic showing the behavioral procedures employed in this experiment. (B) Freezing during the four trials of extinction training. (C) Representative image taken using Nomarski optics at 10×. Arrow indicates the approximate infusion site in the vlPAG. Expression of phosphorylated ERK in the amygdala (D) and mPFC (E) for rats infused with saline (N = 6, black) or naloxone (N = 6, red) and given four trials of extinction training.
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Figure 5: Opioid receptor blockade does not affect ERK phosphorylation following four trials of extinction. (A) Schematic showing the behavioral procedures employed in this experiment. (B) Freezing during the four trials of extinction training. (C) Representative image taken using Nomarski optics at 10×. Arrow indicates the approximate infusion site in the vlPAG. Expression of phosphorylated ERK in the amygdala (D) and mPFC (E) for rats infused with saline (N = 6, black) or naloxone (N = 6, red) and given four trials of extinction training.

Mentions: To determine whether or not the disruption in ERK phosphorylation by opioid receptor blockade in the vlPAG was specific to extinction learning, we infused rats with SAL or NAL into the vlPAG and exposed them to only four extinction training trials. This experiment allowed us to determine if the decrease in ERK phosphorylation in the amygdala and mPFC seen in the previous experiment following NAL infusion is specific to a procedure that results in the formation of extinction memory or if NAL decreases ERK phosphorylation related to retrieval or reconsolidation of memory. Rats received infusions of SAL or NAL into the vlPAG (Figure 5C) prior to four trials of extinction training (Figure 5A). Both groups of rats in this experiment showed normal levels of freezing to the CS during the extinction training session (Figure 5B). ERK phosphorylation was assessed in the amygdala and mPFC 45 min after the extinction training session. t-Tests comparing the two groups indicate that ERK phosphorylation did not change in either the amygdala (t < 1.0) or mPFC (t < 1.0) following NAL infusion and extinction training with four trials (Figure 5D,E). These data indicate that NAL does not affect ERK phosphorylation using a procedure that results in negligible extinction learning.


Regulation of extinction-related plasticity by opioid receptors in the ventrolateral periaqueductal gray matter.

Parsons RG, Gafford GM, Helmstetter FJ - Front Behav Neurosci (2010)

Opioid receptor blockade does not affect ERK phosphorylation following four trials of extinction. (A) Schematic showing the behavioral procedures employed in this experiment. (B) Freezing during the four trials of extinction training. (C) Representative image taken using Nomarski optics at 10×. Arrow indicates the approximate infusion site in the vlPAG. Expression of phosphorylated ERK in the amygdala (D) and mPFC (E) for rats infused with saline (N = 6, black) or naloxone (N = 6, red) and given four trials of extinction training.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927240&req=5

Figure 5: Opioid receptor blockade does not affect ERK phosphorylation following four trials of extinction. (A) Schematic showing the behavioral procedures employed in this experiment. (B) Freezing during the four trials of extinction training. (C) Representative image taken using Nomarski optics at 10×. Arrow indicates the approximate infusion site in the vlPAG. Expression of phosphorylated ERK in the amygdala (D) and mPFC (E) for rats infused with saline (N = 6, black) or naloxone (N = 6, red) and given four trials of extinction training.
Mentions: To determine whether or not the disruption in ERK phosphorylation by opioid receptor blockade in the vlPAG was specific to extinction learning, we infused rats with SAL or NAL into the vlPAG and exposed them to only four extinction training trials. This experiment allowed us to determine if the decrease in ERK phosphorylation in the amygdala and mPFC seen in the previous experiment following NAL infusion is specific to a procedure that results in the formation of extinction memory or if NAL decreases ERK phosphorylation related to retrieval or reconsolidation of memory. Rats received infusions of SAL or NAL into the vlPAG (Figure 5C) prior to four trials of extinction training (Figure 5A). Both groups of rats in this experiment showed normal levels of freezing to the CS during the extinction training session (Figure 5B). ERK phosphorylation was assessed in the amygdala and mPFC 45 min after the extinction training session. t-Tests comparing the two groups indicate that ERK phosphorylation did not change in either the amygdala (t < 1.0) or mPFC (t < 1.0) following NAL infusion and extinction training with four trials (Figure 5D,E). These data indicate that NAL does not affect ERK phosphorylation using a procedure that results in negligible extinction learning.

Bottom Line: The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) in brain regions that likely participate in the consolidation of extinction learning.Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training.These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Wisconsin-Milwaukee Milwaukee, WI, USA.

ABSTRACT
Recent work has led to a better understanding of the neural mechanisms underlying the extinction of Pavlovian fear conditioning. Long-term synaptic changes in the medial prefrontal cortex (mPFC) are critical for extinction learning, but very little is currently known about how the mPFC and other brain areas interact during extinction. The current study examined the effect of drugs that impair the extinction of fear conditioning on the activation of the extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) in brain regions that likely participate in the consolidation of extinction learning. Inhibitors of opioid and N-methyl-d-aspartic acid (NMDA) receptors were applied to the ventrolateral periaqueductal gray matter (vlPAG) and amygdala shortly before extinction training. Results from these experiments show that blocking opioid receptors in the vlPAG prevented the formation of extinction memory, whereas NMDA receptor blockade had no effect. Conversely, blocking NMDA receptors in the amygdala disrupted the formation of fear extinction memory, but opioid receptor blockade in the same brain area did not. Subsequent experiments tested the effect of these drug treatments on the activation of the ERK/MAPK signaling pathway in various brain regions following extinction training. Only opioid receptor blockade in the vlPAG disrupted ERK phosphorylation in the mPFC and amygdala. These data support the idea that opiodergic signaling derived from the vlPAG affects plasticity across the brain circuit responsible for the formation of extinction memory.

No MeSH data available.


Related in: MedlinePlus