Restoration of Morphine-Induced Alterations in Rat Submandibular Gland Function by N-Methyl-D-Aspartate Agonist


The effects of morphine, 1-aminocyclobutane-cis-1,3-dicarboxylic (ACBD; NMDA agonist) and 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphoric acid (CPP; NMDA antagonist) and their concurrent therapy on rat submandibular secretory function were studied. Pure submandibular saliva was collected intra-orally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Intraperitoneal injection of morphine (6 mg/kg) induced significant inhibition of salivary flow rate, total protein, calcium, and TGF-β1 concentrations. Administration of ACBD (10 mg/kg) and CPP (10 mg/kg) alone did not influence secretion of submandibular glands. In combination therapy, coadministration of CPP with morphine did not influence morphine-induced changes in salivary function while ABCD could restore all morphine-induced changes. In combination treatment, ACBD prevented morphine-induced reduction of flow rate, total protein, calcium, and TGF-β1 and reached control levels. It is concluded that morphine-induced alterations in submandibular gland function are mediated through NMDA receptors.


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This work was supported by a grant from National Excellency of Toxicology and Food Chemistry, TUMS.

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Hashemi, N., Mohammadirad, A., Bayrami, Z. et al. Restoration of Morphine-Induced Alterations in Rat Submandibular Gland Function by N-Methyl-D-Aspartate Agonist. BIOLOGIA FUTURA 57, 283–294 (2006).

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  • 1-aminocyclobutane-cis-1,3-dicarboxylic
  • 3-((R)-2-carboxypiperazin-4-yl)-propyl-1-phosphoric acid
  • N-methyl-D-aspartate
  • morphine
  • submandibular gland
  • saliva