Dataset Information

Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.

ABSTRACT: Alterations of long-term synaptic plasticity have been proposed to participate in the development of addiction. To preserve synaptic functions, homeostatic processes must be engaged after exposure to abused drugs. At the mouse cortico-accumbens synapses, a single in vivo injection of Delta9-tetrahydrocannabinol (THC) suppresses endocannabinoid-mediated long-term depression. Using biochemical and electrophysiological approaches, we now report that 1 week of repeated in vivo THC treatment reduces the coupling efficiency of cannabinoid CB1 receptors (CB1Rs) to G(i/o) transduction proteins, as well as CB1R-mediated inhibition of excitatory synaptic transmission at the excitatory synapses between the prefrontal cortex and the nucleus accumbens (NAc). Nonetheless, we found that cortico-accumbens synapses unexpectedly express normal long-term depression because of a reversible switch in its underlying mechanisms. The present data show that, in THC-treated mice, long-term depression is expressed because a presynaptic mGluR2/3 (metabotropic glutamate receptor 2/3)-dependent mechanism replaces the impaired endocannabinoid system. Thus, in the NAc, a novel form of presynaptic homeostasis rescues synaptic plasticity from THC-induced deficits.

SUBMITTER: Mato S

PROVIDER: S-EPMC6726043 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.

Mato Susana S Robbe David D Puente Nagore N Grandes Pedro P Manzoni Olivier J OJ

The Journal of neuroscience : the official journal of the Society for Neuroscience 20051201 50

Alterations of long-term synaptic plasticity have been proposed to participate in the development of addiction. To preserve synaptic functions, homeostatic processes must be engaged after exposure to abused drugs. At the mouse cortico-accumbens synapses, a single in vivo injection of Delta9-tetrahydrocannabinol (THC) suppresses endocannabinoid-mediated long-term depression. Using biochemical and electrophysiological approaches, we now report that 1 week of repeated in vivo THC treatment reduces ...[more]

PMID: 16354920

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Project description:Background: Adolescent cannabis use leads to long-lasting behavioral changes involving cognitive and reward processes. However, the underlying molecular mechanisms are not well understood. To address this limitation, we performed gene network analyses using transcriptomic data from mice exposed during adolescence to Δ-9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis. Methods: We injected vehicle or THC in female and male mice during the entire adolescence period. Two weeks following the last exposure, we measured recognition memory, social interaction and anxiety-related behaviors. We generated 120 RNA-seq datasets from 5 brain regions for each mouse. We performed differential gene expression analysis and constructed co-expression networks to identify THC-induced transcriptional alterations at the level of individual genes, gene networks, biological pathways, and cellular specificity. Further, we integrated THC-correlated gene networks with human traits from genome-wide association studies and performed key driver analysis to identify potential regulators of disorder-associated networks. Results: THC impaired cognitive behaviors of mice, with memory being more impacted in females, which coincided with larger transcriptional alterations in the female brain. Gene network analyses identified brain region-, cell type- and sex- specific co-expressed genes (“modules”) dysregulated by THC. THC-induced memory deficits in females were correlated with disruption of gene networks involved in endocannabinoid signaling and inflammation. Additional THC-correlated modules in both sexes involved converging pathways related to dopamine signaling and addiction processes. Moreover, the connectivity map of THC-correlated modules uncovered intra- and inter-region molecular circuitries influenced by THC. Further, modules altered by THC treatment were enriched in genes relevant for human cognition and schizophrenia. Conclusions: These findings provide novel insights concerning the genes, cell types, and pathways underlying persistent behavioral deficits induced by adolescent exposure to THC in a sex-specific manner, and highlight the connection between adolescent cannabis use and neuropsychiatric disorders in humans.

Dataset Information

Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.

Publications

Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.

Similar Datasets

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