Clinical Neuroscience

[MOLECULAR ARCHITECTURE OF THE CANNABINOID SIGNALING SYSTEM IN THE CORE OF THE NUCLEUS ACCUMBENS]

MÁTYÁS Ferenc1, WATANABE Masahiko2, MACKIE Ken3, KATONA István1, FREUND F. Tamás1

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction- related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb) - which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachidonoyl- glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-α), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-α and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-α distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals forming excitatory synapses on these spineheads were found to express CB1 receptors. Our results demonstrate that the molecular constituents for a retrograde endocannabinoid control of glutamatergic transmission are available in the core of the nAcb, and their relative subcellular location is consistent with a role of 2-AG in addiction-related plasticity of cortical excitatory synapses in this reward area.]

AFFILIATIONS

  1. Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest
  2. Department of Anatomy, Hokkaido University School of Medicine, Sapporo
  3. Department of Anesthesiology, University of Washington, Seattle, Washington

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