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A single in-vivo exposure to Δ9THC blocks endocannabinoid-mediated synaptic plasticity


Endogenous cannabinoids (eCB) mediate synaptic plasticity in brain regions involved in learning and reward. Here we show that in mice, a single in-vivo exposure to Δ9-tetrahydrocannabinol (THC) abolishes the retrograde signaling that underlies eCB-mediated synaptic plasticity in both nucleus accumbens (NAc) and hippocampus in vitro. This effect is reversible within 3 days and is associated with a transient modification in the functional properties of cannabinoid receptors.

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Figure 1: Single in-vivo administration of THC abolishes eCB-mediated synaptic plasticity in NAc and hippocampus.
Figure 2: THC single injection causes functional tolerance.


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Work in O.J.M.'s laboratory is supported by grants from INSERM, Ministère de la Recherche, Fondation pour le Recherche Médicale and Région Aquitaine. P.E.C.'s laboratory is supported by grants from NIH (National Institute on Drug Abuse) and the Pew Charitable Trust.

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Correspondence to Pablo E Castillo or Olivier J Manzoni.

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Supplementary information

Supplementary Fig. 1

In both the Nac and the CA1 region of the hippocampus, a single THC injection (3 mg/kg) is not sufficient to uncouple CB1R from Gi/o proteins. CB1R-stimulation of [35S]GTPγS binding with the CB-agonist WIN55,212-2 (100μM) in the NAc and hippocampus CA1 demonstrates unaltered cannabinoid agonist-stimulated activation of Gi/o proteins after single THC exposure (vehicle white bars; THC black bars). Coincubation in the presence of SR141716-A (10μM) prevented the stimulatory effect of WIN55,212-2 (100μM) in sections from both groups indicating the involvement of CB1Rs (not shown). (PDF 38 kb)

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Mato, S., Chevaleyre, V., Robbe, D. et al. A single in-vivo exposure to Δ9THC blocks endocannabinoid-mediated synaptic plasticity. Nat Neurosci 7, 585–586 (2004).

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