AIMS: Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc. METHODS: Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis. RESULTS: Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc. CONCLUSION: Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc.
AIMS: Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc. METHODS: Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis. RESULTS: Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc. CONCLUSION: Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc.
Authors: G Di Chiara; G Tanda; V Bassareo; F Pontieri; E Acquas; S Fenu; C Cadoni; E Carboni Journal: Ann N Y Acad Sci Date: 1999-06-29 Impact factor: 5.691
Authors: Greg I Elmer; Jeanne O Pieper; Marcelo Rubinstein; Malcolm J Low; David K Grandy; Roy A Wise Journal: J Neurosci Date: 2002-05-10 Impact factor: 6.167
Authors: G I Elmer; J O Pieper; J Levy; M Rubinstein; M J Low; D K Grandy; R A Wise Journal: Psychopharmacology (Berl) Date: 2005-09-29 Impact factor: 4.530
Authors: Gilles Martin; Ana Guadaño-Ferraz; Beatriz Morte; Serge Ahmed; George F Koob; Luis De Lecea; George R Siggins Journal: J Pharmacol Exp Ther Date: 2004-07-19 Impact factor: 4.030
Authors: Amanda K Fakira; George S Portugal; Brianna Carusillo; Zare Melyan; Jose A Morón Journal: Biol Psychiatry Date: 2013-06-02 Impact factor: 13.382
Authors: Bruna A Girardi; Shaiana Fabbrin; Arithane L Wendel; Carlos F Mello; Maribel A Rubin Journal: Psychopharmacology (Berl) Date: 2019-12-11 Impact factor: 4.530