Previous studies have indicated that excitatory amino acids are involved in the analgesic and addictive properties of morphine. However, their role in the morphine-induced alterations in glucose metabolism is not known. This study assessed the contribution of NMDA receptor activation to the morphine-induced hormonal and metabolic alterations in conscious unrestrained chronically catheterized rats. Whole body glucose flux was assessed with a primed constant intravenous infusion of [3-3H]glucose in rats pretreated with the NMDA-receptor antagonist MK-801 (0.25 mg/kg, intraarterial) or an equal volume (1.5 ml) of sterile saline (0.9%) administered 15 min prior to i.c.v. injection of H2O (Con; 5 μl) or morphine sulfate (80 μg). No significant alterations were noted in metabolic and hormonal parameters of H2O injected rats. i.c.v. morphine increased the plasma glucose concentration (60%), hepatic glucose production (R(a); 60%) and whole body glucose utilization (R(d); 53%), but did not alter the glucose metabolic clearance rate (MCR). MK-801 alone resulted in transient hyperglycemia (25%), stimulation of glucose R(a) (60%) and glucose R(d) (53%), and a significant (30%) increase in MCR. MK-801 pretreatment blunted the morphine-induced hyperglycemia and the increased glucose R(a) and R(d). Morphine increased the plasma concentration of epinephrine (4-fold), norepinephrine (2-fold) and corticosterone (67%); however, no alterations in plasma insulin and glucagon were detected. MK-801 pretreatment, blunted the morphine-induced increase in corticosterone and norepinephrine, and elicited a significant rise in insulin concentrations. These results indicate that activation of the NMDA receptors contributes to the morphine-induced hyperglycemia and hormonal alterations. Furthermore, this response appears partially mediated by activation of sympathetic outflow and suppression of insulin release, which is blunted by inhibition of NMDA receptors.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology