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

• Published in: The international journal of neuropsychopharmacology 2015-02, Vol.18 (4), p.pyu052-pyu052
• Main Authors: Zhang, Xiaoqun, Feng, Ze-Jun, Chergui, Karima
• Format: Article
• Language: English
• Subjects: Animals; Benzoxazines - pharmacology; Cannabinoid Receptor Agonists - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - growth & development; Corpus Striatum - physiology; Electric Stimulation; Excitatory Amino Acid Agonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Glycine - analogs & derivatives; Glycine - pharmacology; Long-Term Synaptic Depression - drug effects; Long-Term Synaptic Depression - physiology; Male; Medicin och hälsovetenskap; Mice, Inbred C57BL; Morpholines - pharmacology; Naphthalenes - pharmacology; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - metabolism; Nucleus Accumbens - drug effects; Nucleus Accumbens - growth & development; Nucleus Accumbens - physiology; Receptor, Cannabinoid, CB1 - metabolism; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - metabolism; Resorcinols - pharmacology; Tissue Culture Techniques
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1093/ijnp/pyu052

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.