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Traumatic stress reactivity promotes excessive alcohol drinking and alters the balance of prefrontal cortex-amygdala activity.

Edwards S, Baynes BB, Carmichael CY, Zamora-Martinez ER, Barrus M, Koob GF, Gilpin NW - Transl Psychiatry (2013)

Bottom Line: The aim of these studies was to examine the effects of traumatic stress (and stress reactivity) on alcohol-related behaviors and neuronal activation patterns.Furthermore, activity of upstream regions was differentially predictive of downstream regional activity in the Avoiders versus Non-Avoiders.An animal model for assessing the effect of traumatic stress on alcohol drinking reveals individual differences in neuronal activation patterns associated with re-exposure to traumatic stress-related stimuli, and may provide insight into the neural mechanisms underlying excessive alcohol consumption in humans with PTSD.

View Article: PubMed Central - PubMed

Affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.

ABSTRACT
Post-traumatic stress disorder (PTSD) and alcoholism are highly comorbid in humans and have partially overlapping symptomatic profiles. The aim of these studies was to examine the effects of traumatic stress (and stress reactivity) on alcohol-related behaviors and neuronal activation patterns. Male Wistar rats were trained to respond for alcohol, were exposed to predator odor (bobcat urine) paired with context and were tested for short- and long-term avoidance of the predator odor-paired context, alcohol self-administration and compulsivity of alcohol responding. Rats were re-exposed to the odor-paired context for western blot analysis of ERK phosphorylation in subregions of the medial prefrontal cortex (mPFC) and the amygdala. Rats that avoided the predator-paired chamber (Avoiders) exhibited persistent avoidance up to 6 weeks post conditioning. Avoiders exhibited increases in operant alcohol responding over weeks, as well as more compulsive-like responding for alcohol adulterated with quinine. Following re-exposure to the predator odor-paired context, Avoiders and Non-Avoiders exhibited unique patterns of neuronal activation in subregions of the mPFC and the amygdala, which were correlated with changes in avoidance and alcohol drinking. Furthermore, activity of upstream regions was differentially predictive of downstream regional activity in the Avoiders versus Non-Avoiders. An animal model for assessing the effect of traumatic stress on alcohol drinking reveals individual differences in neuronal activation patterns associated with re-exposure to traumatic stress-related stimuli, and may provide insight into the neural mechanisms underlying excessive alcohol consumption in humans with PTSD.

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Related in: MedlinePlus

Within-subject between-region correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context. (a) In Avoiders (left panel), but not in Non-Avoiders (right panel) or Controls (data not shown), there was a significant correlation between dorsomedial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) ERK phosphorylation (pERK) expression. Panel b reports the strength and direction of correlations between pERK expression in ventromedial PFC (vmPFC) and central nucleus of the amygdala (CeA; top row), and also between BLA and CeA (bottom row) in Avoiders, Non-Avoiders and Controls upon re-exposure to predator odor-paired context.
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fig3: Within-subject between-region correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context. (a) In Avoiders (left panel), but not in Non-Avoiders (right panel) or Controls (data not shown), there was a significant correlation between dorsomedial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) ERK phosphorylation (pERK) expression. Panel b reports the strength and direction of correlations between pERK expression in ventromedial PFC (vmPFC) and central nucleus of the amygdala (CeA; top row), and also between BLA and CeA (bottom row) in Avoiders, Non-Avoiders and Controls upon re-exposure to predator odor-paired context.

Mentions: At the end of behavioral testing, animals were exposed to a final 15-min exposure to the predator-paired context (neutral context in unstressed controls) and were killed, and the brains were removed for western blot analysis to measure context-associated ERK phosphorylation. As illustrated in Figure 2a, a two-way (group × medial prefrontal cortex (mPFC) region) ANOVA revealed a significant interaction effect on pERK levels, F(2,98)=3.25, P<0.05, and post-hoc analyses indicated that pERK levels in ventromedial PFC (vmPFC) were significantly higher in Avoiders relative to Non-Avoiders (P<0.01). A separate two-way (group × mPFC region) ANOVA of data only from the stressed groups (data normalized to controls) revealed a significant interaction effect on pERK, F(1,64)=5.55, P<0.05), and post-hoc analyses indicated that normalized pERK levels were significantly higher in vmPFC versus dorsomedial PFC (dmPFC) of Avoiders (P<0.05). As illustrated in Figure 2b, a two-way (group × amygdala region) ANOVA of data only from the stressed groups (data normalized to controls) revealed a significant main effect of region on pERK, F(1,63)=8.15, P<0.01), which indicated that Avoider and Non-Avoider groups exhibited collectively higher pERK expression in the central nucleus of the amygdala (CeA) versus basolateral amygdala (BLA). In accordance with subgroup data, avoidance of the odor-paired environment was significantly correlated with vmPFC pERK levels (r2=0.17, P<0.05). We next determined within-subject, inter-regional correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context (Figure 3). Significant correlations were found between BLA and CeA in both Avoiders (r2=0.46, P<0.01) and Non-Avoiders (r2=0.42, P<0.05), but not in stress-naive controls (r2=0.19, P=0.21). Furthermore, in Avoiders, but not in Non-Avoiders or Controls, there was a significant correlation between dmPFC and BLA (r2=0.68, P<0.01) and a marginally non-significant correlation between vmPFC and CeA (r2=0.20, P=0.06). In most cases, inter-regional correlations were bidirectional, that is, correlative data comprised both increases and decreases in ERK phosphorylation.


Traumatic stress reactivity promotes excessive alcohol drinking and alters the balance of prefrontal cortex-amygdala activity.

Edwards S, Baynes BB, Carmichael CY, Zamora-Martinez ER, Barrus M, Koob GF, Gilpin NW - Transl Psychiatry (2013)

Within-subject between-region correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context. (a) In Avoiders (left panel), but not in Non-Avoiders (right panel) or Controls (data not shown), there was a significant correlation between dorsomedial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) ERK phosphorylation (pERK) expression. Panel b reports the strength and direction of correlations between pERK expression in ventromedial PFC (vmPFC) and central nucleus of the amygdala (CeA; top row), and also between BLA and CeA (bottom row) in Avoiders, Non-Avoiders and Controls upon re-exposure to predator odor-paired context.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756295&req=5

fig3: Within-subject between-region correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context. (a) In Avoiders (left panel), but not in Non-Avoiders (right panel) or Controls (data not shown), there was a significant correlation between dorsomedial prefrontal cortex (dmPFC) and basolateral amygdala (BLA) ERK phosphorylation (pERK) expression. Panel b reports the strength and direction of correlations between pERK expression in ventromedial PFC (vmPFC) and central nucleus of the amygdala (CeA; top row), and also between BLA and CeA (bottom row) in Avoiders, Non-Avoiders and Controls upon re-exposure to predator odor-paired context.
Mentions: At the end of behavioral testing, animals were exposed to a final 15-min exposure to the predator-paired context (neutral context in unstressed controls) and were killed, and the brains were removed for western blot analysis to measure context-associated ERK phosphorylation. As illustrated in Figure 2a, a two-way (group × medial prefrontal cortex (mPFC) region) ANOVA revealed a significant interaction effect on pERK levels, F(2,98)=3.25, P<0.05, and post-hoc analyses indicated that pERK levels in ventromedial PFC (vmPFC) were significantly higher in Avoiders relative to Non-Avoiders (P<0.01). A separate two-way (group × mPFC region) ANOVA of data only from the stressed groups (data normalized to controls) revealed a significant interaction effect on pERK, F(1,64)=5.55, P<0.05), and post-hoc analyses indicated that normalized pERK levels were significantly higher in vmPFC versus dorsomedial PFC (dmPFC) of Avoiders (P<0.05). As illustrated in Figure 2b, a two-way (group × amygdala region) ANOVA of data only from the stressed groups (data normalized to controls) revealed a significant main effect of region on pERK, F(1,63)=8.15, P<0.01), which indicated that Avoider and Non-Avoider groups exhibited collectively higher pERK expression in the central nucleus of the amygdala (CeA) versus basolateral amygdala (BLA). In accordance with subgroup data, avoidance of the odor-paired environment was significantly correlated with vmPFC pERK levels (r2=0.17, P<0.05). We next determined within-subject, inter-regional correlations of ERK phosphorylation upon re-exposure to the predator odor-paired context (Figure 3). Significant correlations were found between BLA and CeA in both Avoiders (r2=0.46, P<0.01) and Non-Avoiders (r2=0.42, P<0.05), but not in stress-naive controls (r2=0.19, P=0.21). Furthermore, in Avoiders, but not in Non-Avoiders or Controls, there was a significant correlation between dmPFC and BLA (r2=0.68, P<0.01) and a marginally non-significant correlation between vmPFC and CeA (r2=0.20, P=0.06). In most cases, inter-regional correlations were bidirectional, that is, correlative data comprised both increases and decreases in ERK phosphorylation.

Bottom Line: The aim of these studies was to examine the effects of traumatic stress (and stress reactivity) on alcohol-related behaviors and neuronal activation patterns.Furthermore, activity of upstream regions was differentially predictive of downstream regional activity in the Avoiders versus Non-Avoiders.An animal model for assessing the effect of traumatic stress on alcohol drinking reveals individual differences in neuronal activation patterns associated with re-exposure to traumatic stress-related stimuli, and may provide insight into the neural mechanisms underlying excessive alcohol consumption in humans with PTSD.

View Article: PubMed Central - PubMed

Affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.

ABSTRACT
Post-traumatic stress disorder (PTSD) and alcoholism are highly comorbid in humans and have partially overlapping symptomatic profiles. The aim of these studies was to examine the effects of traumatic stress (and stress reactivity) on alcohol-related behaviors and neuronal activation patterns. Male Wistar rats were trained to respond for alcohol, were exposed to predator odor (bobcat urine) paired with context and were tested for short- and long-term avoidance of the predator odor-paired context, alcohol self-administration and compulsivity of alcohol responding. Rats were re-exposed to the odor-paired context for western blot analysis of ERK phosphorylation in subregions of the medial prefrontal cortex (mPFC) and the amygdala. Rats that avoided the predator-paired chamber (Avoiders) exhibited persistent avoidance up to 6 weeks post conditioning. Avoiders exhibited increases in operant alcohol responding over weeks, as well as more compulsive-like responding for alcohol adulterated with quinine. Following re-exposure to the predator odor-paired context, Avoiders and Non-Avoiders exhibited unique patterns of neuronal activation in subregions of the mPFC and the amygdala, which were correlated with changes in avoidance and alcohol drinking. Furthermore, activity of upstream regions was differentially predictive of downstream regional activity in the Avoiders versus Non-Avoiders. An animal model for assessing the effect of traumatic stress on alcohol drinking reveals individual differences in neuronal activation patterns associated with re-exposure to traumatic stress-related stimuli, and may provide insight into the neural mechanisms underlying excessive alcohol consumption in humans with PTSD.

Show MeSH
Related in: MedlinePlus