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Altered Corticolimbic Control of the Nucleus Accumbens by Long-term Δ9-Tetrahydrocannabinol Exposure

  • Eun-Kyung Hwang
    Affiliations
    Electrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland
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  • Carl R. Lupica
    Correspondence
    Address correspondence to Carl Lupica, Ph.D., Chief, Electrophysiology Research Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224.
    Affiliations
    Electrophysiology Research Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland
    Search for articles by this author

      Abstract

      Background

      The decriminalization and legalization of cannabis and the expansion of availability of medical cannabis in North America have led to an increase in cannabis use and the availability of high-potency strains. Cannabis potency is determined by the concentration of Δ9-tetrahydrocannabinol (Δ9-THC), a psychoactive constituent that activates cannabinoid CB1 and CB2 receptors. The use of high-potency cannabis is associated with cannabis use disorder and increased susceptibility to psychiatric illness. The nucleus accumbens (NAc) is part of a brain reward circuit affected by Δ9-THC through modulation of glutamate afferents arising from corticolimbic brain areas implicated in drug addiction and psychiatric disorders. Moreover, brain imaging studies show alterations in corticolimbic and NAc properties in human cannabis users.

      Methods

      Using in vitro electrophysiology and optogenetics, we examined how Δ9-THC alters corticolimbic input to the NAc in rats.

      Results

      We found that long-term exposure to Δ9-THC weakens prefrontal cortex glutamate input to the NAc shell and strengthens input from basolateral amygdala and ventral hippocampus. Further, whereas long-term exposure to Δ9-THC had no effect on net strength of glutamatergic input to NAc shell arising from midbrain dopamine neurons, it alters fundamental properties of these synapses.

      Conclusions

      Long-term exposure to Δ9-THC shifts control of the NAc shell from cortical to limbic input, likely contributing to cognitive and psychiatric dysfunction that is associated with cannabis use.

      Keywords

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