title: Induction of cannabinoid- and N-methyl-D-aspartate receptor-mediated long-term depression in the nucleus accumbens and dorsolateral striatum is region and age dependent.
abstract: BACKGROUND
  The adolescent brain is sensitive to experience-dependent plasticity and might be more vulnerable than the adult brain to the effects of some drugs of abuse. The factors that contribute to these differences are not fully identified. We have examined the ability of cannabinoids to induce a form of synaptic plasticity, long-term depression, in the nucleus accumbens and dorsolateral striatum of adolescent and adult mice.
  
  
  METHODS
  We measured field excitatory postsynaptic potentials/population spikes in brain slices.
  
  
  RESULTS
  We found that the cannabinoid receptor agonist WIN 55,212-2 (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate) induced long-term depression in the nucleus accumbens of adolescent but not adult mice and failed to induce long-term depression in the dorsolateral striatum of adolescent or adult mice. Similar results were obtained with the group I metabotropic glutamate receptor agonist (S)-3,5- dihydroxyphenylglycine, which has previously been shown to promote the release of endocannabinoids. These age-related differences were associated with reduced protein levels of the cannabinoid type 1 receptor and metabotropic glutamate receptor 1 in adult nucleus accumbens and dorsolateral striatum and with an increased tone of endocannabinoids in the dorsolateral striatum of adult mice. We also found that N-methyl-D-aspartate receptor-dependent long-term depression, which was induced in the nucleus accumbens of adolescent mice, was blunted in adult mice, possibly because of decreased levels of GluN1, the obligatory subunit of N-methyl-D-aspartate receptors.
  
  
  CONCLUSIONS
  This study identifies region- and age-specific differences in the ability of endogenous and exogenous cannabinoids, and of N-methyl-D-aspartate receptors, to induce long-term depression in the striatal complex. These observations might contribute to a better understanding of the increased sensitivity of the adolescent brain to drug induced-plasticity.
authors.affiliation: The Karolinska Institute, Department of Physiology and Pharmacology, Section of Molecular Neurophysiology, Von Eulers väg 8, 171 77 Stockholm, Sweden (Drs Zhang, Feng, and Chergui).
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Karolinska Institute, Department of Physiology and Pharmacology, Section of Molecular Neurophysiology, Von Eulers väg 8, 171 77 Stockholm, Sweden (Drs Zhang, Feng, and Chergui).
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Feng
authors.affiliation: The Karolinska Institute, Department of Physiology and Pharmacology, Section of Molecular Neurophysiology, Von Eulers väg 8, 171 77 Stockholm, Sweden (Drs Zhang, Feng, and Chergui). karima.chergui@ki.se.
authors.forename: Karima
authors.initials: K
authors.lastname: Chergui
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D046509:Tissue Culture Techniques
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D018690:Excitatory Amino Acid Agonists; C121673:Gprin1 protein, mouse; D009025:Morpholines; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D043884:Receptor, Cannabinoid, CB1; D016194:Receptors, N-Methyl-D-Aspartate; D012118:Resorcinols; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine
keywords: age; endocannabinoids; long-term depression; nucleus accumbens; striatum