Differential effects of subcutaneous and intrathecal morphine administration on blood glucose in mice: comparison with intracerebroventricular administration.

The s.c. administration of morphine (2.5-80 mg/kg) produced a dose-dependent hyperglycemia, whereas morphine (12.5-50 micrograms) given i.t. in the lumbar region caused a dose-dependent hypoglycemia in unanesthetized mice. Both effects on blood glucose were antagonized by s.c. naloxone, although inhibition of i.t. morphine required a higher naloxone dose. Naloxone pretreatment with 2 mg/kg, but not 1 mg/kg s.c., potentiated a hyperglycemic response to i.t. saline. High i.t. doses of morphine caused an early (within 2 min) scratching behavior that was not inhibited by naloxone or glucose loading and a later (greater than 20 min) tonic convulsive behavior (opisthotonus). Lethality was partially inhibited by glucose loading which delayed, but did not prevent, the hypoglycemic effect of i.t. morphine. The hypoglycemic effect of i.t. morphine was also delayed in streptozotocin-diabetic ICR mice and diabetic (db/db) C57BL/KsJ mice, but the latter were more sensitive to lethality, which occurred without hypoglycemia or seizures. All these effects of i.t. morphine were completely blocked by acute spinal transection of T10-T11, but the nociceptive, hypoglycemic and opisthotonic effects were not mimicked by i.c.v. morphine (6.25-50 micrograms) in ICR mice, which showed a bell-shaped hyperglycemic dose-response relationship and a brief explosive motor behavior at the higher doses (25-50 micrograms). It is concluded that the effects of morphine on blood glucose and on behavior are dependent upon the route of administration, and that the convulsive effect of i.t. morphine may be facilitated by the production of a profound hypoglycemia, which involves a spinal, rather than supraspinal or systemic, action of morphine.