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Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

Zschenderlein C, Gebhardt C, von Bohlen Und Halbach O, Kulisch C, Albrecht D - PLoS ONE (2011)

Bottom Line: Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala.The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis.In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, CVK, Berlin, Germany.

ABSTRACT
The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

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The CB1 receptor is involved in the mediation of capsaicin-induced inhibition of LA-LTP.(A) The CB1 receptor antagonist AM251 (2.5 µM) evoked a reduction of LA-LTP in comparison with controls. This reduction was not enhanced by capsaicin. In contrast, the co-administration of AM251 and capsaicin (1, 10 µM) caused an increase in the magnitude of HFS-induced LA-LTP. (B) Bar histogram of data points averaged 57 to 60 min after HFS and normalized with respect to baseline (mean ± SEM). Significant differences are indicated. *p<0.05, **p<0.01. (C) Anandamide (1 µM, 10 µM) provoked a significant suppression of LA-LTP. Representative traces were recorded 5 min prior to tetanus (dashed lines) and 60 min after tetanus (solid lines). Data were obtained by using horizontal slices derived from adult mice.
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pone-0016116-g006: The CB1 receptor is involved in the mediation of capsaicin-induced inhibition of LA-LTP.(A) The CB1 receptor antagonist AM251 (2.5 µM) evoked a reduction of LA-LTP in comparison with controls. This reduction was not enhanced by capsaicin. In contrast, the co-administration of AM251 and capsaicin (1, 10 µM) caused an increase in the magnitude of HFS-induced LA-LTP. (B) Bar histogram of data points averaged 57 to 60 min after HFS and normalized with respect to baseline (mean ± SEM). Significant differences are indicated. *p<0.05, **p<0.01. (C) Anandamide (1 µM, 10 µM) provoked a significant suppression of LA-LTP. Representative traces were recorded 5 min prior to tetanus (dashed lines) and 60 min after tetanus (solid lines). Data were obtained by using horizontal slices derived from adult mice.

Mentions: Outside the brain anandamide significantly decreases NOS activity via CB1 receptors, whereas TRPV1 stimulation by anandamide enhances NOS activity [45]. To get insight into a comparable mechanism within the brain, we used the CB1 receptor antagonist AM251 (2.5 µM) for further experiments in horizontal slices. As shown in Fig. 6A and B, AM251 suppressed HFS-induced LA-LTP. However, co-application of AM251 and capsaicin reduced the inhibitory effect of capsaicin on the magnitude of LA-LTP (AM251: 108.8±4.3% [n = 9] vs. AM251 +1 µM cap: 126.8±2.8% [n = 10] vs. AM251+10 µM cap: 120.9±3.5% [n = 8], p<0.05). This suggests that the suppressive effect of capsaicin on LA-LTP might be mediated by the synthesis of anandamide or other endocannabinoids and the activation of CB1 receptors. Furthermore, application of anandamide (1 µM: 117.5±2.2% [n = 11], 10 µM: 110.4±5.5% [n = 12]) caused the same inhibitory effect as capsaicin on LA-LTP (Fig. 6C). We found similar results with N-oleoyldopamine (OLDA) (data not shown), a bioactive lipid originally found in the mammalian brain. This endovanilloid selectively activates the TRPV1 channel.


Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1.

Zschenderlein C, Gebhardt C, von Bohlen Und Halbach O, Kulisch C, Albrecht D - PLoS ONE (2011)

The CB1 receptor is involved in the mediation of capsaicin-induced inhibition of LA-LTP.(A) The CB1 receptor antagonist AM251 (2.5 µM) evoked a reduction of LA-LTP in comparison with controls. This reduction was not enhanced by capsaicin. In contrast, the co-administration of AM251 and capsaicin (1, 10 µM) caused an increase in the magnitude of HFS-induced LA-LTP. (B) Bar histogram of data points averaged 57 to 60 min after HFS and normalized with respect to baseline (mean ± SEM). Significant differences are indicated. *p<0.05, **p<0.01. (C) Anandamide (1 µM, 10 µM) provoked a significant suppression of LA-LTP. Representative traces were recorded 5 min prior to tetanus (dashed lines) and 60 min after tetanus (solid lines). Data were obtained by using horizontal slices derived from adult mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3020947&req=5

pone-0016116-g006: The CB1 receptor is involved in the mediation of capsaicin-induced inhibition of LA-LTP.(A) The CB1 receptor antagonist AM251 (2.5 µM) evoked a reduction of LA-LTP in comparison with controls. This reduction was not enhanced by capsaicin. In contrast, the co-administration of AM251 and capsaicin (1, 10 µM) caused an increase in the magnitude of HFS-induced LA-LTP. (B) Bar histogram of data points averaged 57 to 60 min after HFS and normalized with respect to baseline (mean ± SEM). Significant differences are indicated. *p<0.05, **p<0.01. (C) Anandamide (1 µM, 10 µM) provoked a significant suppression of LA-LTP. Representative traces were recorded 5 min prior to tetanus (dashed lines) and 60 min after tetanus (solid lines). Data were obtained by using horizontal slices derived from adult mice.
Mentions: Outside the brain anandamide significantly decreases NOS activity via CB1 receptors, whereas TRPV1 stimulation by anandamide enhances NOS activity [45]. To get insight into a comparable mechanism within the brain, we used the CB1 receptor antagonist AM251 (2.5 µM) for further experiments in horizontal slices. As shown in Fig. 6A and B, AM251 suppressed HFS-induced LA-LTP. However, co-application of AM251 and capsaicin reduced the inhibitory effect of capsaicin on the magnitude of LA-LTP (AM251: 108.8±4.3% [n = 9] vs. AM251 +1 µM cap: 126.8±2.8% [n = 10] vs. AM251+10 µM cap: 120.9±3.5% [n = 8], p<0.05). This suggests that the suppressive effect of capsaicin on LA-LTP might be mediated by the synthesis of anandamide or other endocannabinoids and the activation of CB1 receptors. Furthermore, application of anandamide (1 µM: 117.5±2.2% [n = 11], 10 µM: 110.4±5.5% [n = 12]) caused the same inhibitory effect as capsaicin on LA-LTP (Fig. 6C). We found similar results with N-oleoyldopamine (OLDA) (data not shown), a bioactive lipid originally found in the mammalian brain. This endovanilloid selectively activates the TRPV1 channel.

Bottom Line: Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala.The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis.In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, CVK, Berlin, Germany.

ABSTRACT
The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.

Show MeSH
Related in: MedlinePlus