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Featured ArticleArticles, Behavioral/Systems/Cognitive

Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum

Silvia Rossi, Valentina De Chiara, Alessandra Musella, Hajime Kusayanagi, Giorgia Mataluni, Giorgio Bernardi, Alessandro Usiello and Diego Centonze
Journal of Neuroscience 16 July 2008, 28 (29) 7284-7292; DOI: https://doi.org/10.1523/JNEUROSCI.5346-07.2008
Silvia Rossi
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Valentina De Chiara
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Alessandra Musella
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Hajime Kusayanagi
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Giorgia Mataluni
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Giorgio Bernardi
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Alessandro Usiello
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Diego Centonze
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    Figure 1.

    Stress alters the sensitivity of striatal GABA synapses to the stimulation of cannabinoid CB1 receptors. A , HU210, agonist of CB1 receptors, reduced sIPSC frequency in control mice. This effect was fully prevented by preincubation with the CB1 receptor antagonist AM251. B , The graph shows that the depressant effect of HU210 on sIPSC was attenuated in striatal mice exposed to one session of stress, and it was completely abolished in neurons from mice exposed to stress for 3 and 7 consecutive days. *p < 0.05. C , The electrophysiological traces are examples of voltage-clamp recordings in the presence of TTX showing that HU210 (10 min) failed to reduce mIPSC frequency in a mouse exposed to 3 d of stress. D , The graph shows that HU210 failed to reduce eIPSC amplitude in animals stressed for 3 d, but not in control animals or in mice exposed to one session of stress. Error bars indicate SEM. The traces on the right are examples of eIPSCs recorded in control and stressed mice before (1) and during (2) the application of HU210.

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    Figure 2.

    Effects of time on stress-induced inhibition of HU210 responses. A , B , The graphs show that the reduction of sIPSC frequency ( A ) and of eIPSC amplitude ( B ) induced by HU210 in mice exposed to stress for 3 consecutive days was lost 3 and 7 d after the last stress session. The electrophysiological traces are examples of voltage-clamp recordings showing that HU210 reduces normally sIPSC frequency in striatal neurons 3 and 7 d after stress. Error bars indicate SEM. *p < 0.05.

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    Figure 3.

    Stress does not alter the sensitivity of glutamatergic synapses to HU210 and the sensitivity of GABAergic synapses to baclofen. A , The graph shows that the depressant action of HU210 on sEPSC frequency was similar in control and stressed (three sessions) mice. B , The depressant effect of baclofen on sIPSC frequency was similar in control and stressed (three sessions) mice. Error bars indicate SEM.

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    Figure 4.

    Effects of 3,5-DHPG on GABA transmission in stressed mice. The graph shows the early increase and the late reduction of sIPSC frequency after the application of a group I metabotropic glutamate receptor agonist 3,5-DHPG in control mice. Preincubation with AM251 or three sessions of stress prevented the late endocannabinoid-dependent inhibition of sIPSCs. Error bars indicate SEM. Examples of voltage-clamp recordings of sIPSC before and during the application of 3,5-DHPG in control and stressed mice are shown on the right.

  • Figure 5.
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    Figure 5.

    Blockade of glucocorticoid receptors, natural rewards and cocaine reverse the inhibition of HU210 responses induced by stress. A , The graph shows that pretreatment with RU486, antagonist of glucocorticoid receptors, prevented the effects of three sessions of stress on HU210-induced reduction of sIPSC frequency and that corticosterone treatment mimicked the stress-induced effects. B , The graph shows that natural rewards like wheel running or sucrose drinking were able to rescue the effect of HU210 on sIPSC frequency in mice exposed to 3 d of stress. *p < 0.05. C , The sensitivity of striatal sIPSCs to HU210 was normal in mice receiving a single injection of cocaine after the third session of stress. D , The graph shows that neither 24 h of running wheel or sucrose drinking, nor a single injection of cocaine altered per se the sensitivity of GABA synapses to HU210. Error bars indicate SEM.

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The Journal of Neuroscience: 28 (29)
Journal of Neuroscience
Vol. 28, Issue 29
16 Jul 2008
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Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum
Silvia Rossi, Valentina De Chiara, Alessandra Musella, Hajime Kusayanagi, Giorgia Mataluni, Giorgio Bernardi, Alessandro Usiello, Diego Centonze
Journal of Neuroscience 16 July 2008, 28 (29) 7284-7292; DOI: 10.1523/JNEUROSCI.5346-07.2008

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Chronic Psychoemotional Stress Impairs Cannabinoid-Receptor-Mediated Control of GABA Transmission in the Striatum
Silvia Rossi, Valentina De Chiara, Alessandra Musella, Hajime Kusayanagi, Giorgia Mataluni, Giorgio Bernardi, Alessandro Usiello, Diego Centonze
Journal of Neuroscience 16 July 2008, 28 (29) 7284-7292; DOI: 10.1523/JNEUROSCI.5346-07.2008
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