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The role of the hippocampus in avoidance learning and anxiety vulnerability.

Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC - Front Behav Neurosci (2014)

Bottom Line: In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders.The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction.These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosciences, Rutgers - New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, NJ , USA.

ABSTRACT
The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampus may be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats. Second, the function of the hippocampus in Wistar-Kyoto (WKY) rats was compared to SD rats. The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction. The results of the current study indicate that hippocampal damage in SD rats leads to impaired extinction of avoidance learning similar to WKY rats. Furthermore, WKY rats have reduced hippocampal volume and impaired hippocampal synaptic plasticity as compared to SD rats. These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

No MeSH data available.


Related in: MedlinePlus

ITI responding during the first minute of the intertrial interval (ITI). Hippocampal lesion increased ITI responding during the first minute of the ITI during acquisition and extinction (A). Group differences were not present during the second or third minute of the ITI (not shown). WKY rats showed a trend for increased ITI responding during the first minute of the ITI in the avoidance phase, but not extinction (B). Strain differences were not observed during the second or third minute of the ITI (not shown).
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Figure 3: ITI responding during the first minute of the intertrial interval (ITI). Hippocampal lesion increased ITI responding during the first minute of the ITI during acquisition and extinction (A). Group differences were not present during the second or third minute of the ITI (not shown). WKY rats showed a trend for increased ITI responding during the first minute of the ITI in the avoidance phase, but not extinction (B). Strain differences were not observed during the second or third minute of the ITI (not shown).

Mentions: Intertrial interval responses were analyzed because they represent non-reinforced responses. The number of ITI responses generally increased with training, peaking around session 4 or 5, then leveling off [main effect of session, F(11,484) = 6.02, p < 0.001]. ITI responding was greater in the first minute of the ITI as compared to the second or third minutes [main effect of ITI, F(2,88) = 871.10, p < 0.001]. Whereas the main effect of lesion/strain [F(1,44) = 1.6, p = 0.18] was not significant, the lesion/strain × session × ITI interaction [F(110,968) = 1.54, p = 0.001] did reach significance. In post hoc analysis of each ITI minute, lesion/strain affected the first minute ITI response [lesion/strain × session interaction, F(55,495) = 1.78, p = 0.001; main effect of lesion/strain, F(5,45) = 1.62, p = 0.174] (Figure 3), but not second or third minute ITI responses [main effects, F(5,45) ≤ 1.61, p > 0.171; lesion/strain × session interaction, F(55,495) ≤ 1.17, p > 0.196]. Comparisons made between sham and lesions and between unoperated SD and WKY rats for first minute ITI responses revealed that hippocampal but not entorhinal lesions facilitated responding [main effect, F(1,13) = 8.32, p = 0.013], and strain differences trended toward significance with WKY tending to make more ITI responses than SD rats [session × strain interaction, F(11,154) = 2.42, corrected p = 0.051]. Thus, hippocampal but not entorhinal cortex lesions increased ITI responding during the first, but not second or third, minutes of the ITI (Figure 3A). A similar trend was present for WKY rats as compared to SD rats (Figure 3B).


The role of the hippocampus in avoidance learning and anxiety vulnerability.

Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC - Front Behav Neurosci (2014)

ITI responding during the first minute of the intertrial interval (ITI). Hippocampal lesion increased ITI responding during the first minute of the ITI during acquisition and extinction (A). Group differences were not present during the second or third minute of the ITI (not shown). WKY rats showed a trend for increased ITI responding during the first minute of the ITI in the avoidance phase, but not extinction (B). Strain differences were not observed during the second or third minute of the ITI (not shown).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125878&req=5

Figure 3: ITI responding during the first minute of the intertrial interval (ITI). Hippocampal lesion increased ITI responding during the first minute of the ITI during acquisition and extinction (A). Group differences were not present during the second or third minute of the ITI (not shown). WKY rats showed a trend for increased ITI responding during the first minute of the ITI in the avoidance phase, but not extinction (B). Strain differences were not observed during the second or third minute of the ITI (not shown).
Mentions: Intertrial interval responses were analyzed because they represent non-reinforced responses. The number of ITI responses generally increased with training, peaking around session 4 or 5, then leveling off [main effect of session, F(11,484) = 6.02, p < 0.001]. ITI responding was greater in the first minute of the ITI as compared to the second or third minutes [main effect of ITI, F(2,88) = 871.10, p < 0.001]. Whereas the main effect of lesion/strain [F(1,44) = 1.6, p = 0.18] was not significant, the lesion/strain × session × ITI interaction [F(110,968) = 1.54, p = 0.001] did reach significance. In post hoc analysis of each ITI minute, lesion/strain affected the first minute ITI response [lesion/strain × session interaction, F(55,495) = 1.78, p = 0.001; main effect of lesion/strain, F(5,45) = 1.62, p = 0.174] (Figure 3), but not second or third minute ITI responses [main effects, F(5,45) ≤ 1.61, p > 0.171; lesion/strain × session interaction, F(55,495) ≤ 1.17, p > 0.196]. Comparisons made between sham and lesions and between unoperated SD and WKY rats for first minute ITI responses revealed that hippocampal but not entorhinal lesions facilitated responding [main effect, F(1,13) = 8.32, p = 0.013], and strain differences trended toward significance with WKY tending to make more ITI responses than SD rats [session × strain interaction, F(11,154) = 2.42, corrected p = 0.051]. Thus, hippocampal but not entorhinal cortex lesions increased ITI responding during the first, but not second or third, minutes of the ITI (Figure 3A). A similar trend was present for WKY rats as compared to SD rats (Figure 3B).

Bottom Line: In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders.The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction.These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurosciences, Rutgers - New Jersey Medical School, Rutgers, The State University of New Jersey , Newark, NJ , USA.

ABSTRACT
The hippocampus has been implicated in anxiety disorders and post-traumatic stress disorder (PTSD); human studies suggest that a dysfunctional hippocampus may be a vulnerability factor for the development of PTSD. In the current study, we examined the effect of hippocampal damage in avoidance learning, as avoidance is a core symptom of all anxiety disorders. First, the effect of hippocampal damage on avoidance learning was investigated in outbred Sprague Dawley (SD) rats. Second, the function of the hippocampus in Wistar-Kyoto (WKY) rats was compared to SD rats. The WKY rat is an animal model of behavioral inhibition, a risk factor for anxiety, and demonstrates abnormal avoidance learning, marked by facilitated avoidance acquisition and resistance to extinction. The results of the current study indicate that hippocampal damage in SD rats leads to impaired extinction of avoidance learning similar to WKY rats. Furthermore, WKY rats have reduced hippocampal volume and impaired hippocampal synaptic plasticity as compared to SD rats. These results suggest that hippocampal dysfunction enhances the development of persistent avoidance responding and, thus, may confer vulnerability to the development of anxiety disorders and PTSD.

No MeSH data available.


Related in: MedlinePlus