Behavioral cross-sensitization between morphine-induced locomotion and sodium depletion-induced salt appetite

In general terms, sensitization refers to the capacity of a repetitive stimulus of fixed strength to produce a progressive increase in the magnitude of a response with each stimulation. In the addiction literature cross-sensitization is the capacity of an agent with abuse potential to sensitize a behavioral response induced by another stimulus. In the present experiments we examined the effects of morphine pretreatment on furosemide-induced saline intake and conversely sodium appetite induction on morphine-induced locomotion. In an initial experiment rats were pretreated with morphine (10 mg/kg, s.c.) or vehicle for 5 days. The rats were then sodium or sham depleted and 24 h later given a sodium appetite test. Sodium depleted rats pretreated with morphine increased saline intake compared to depleted rats initially pretreated with vehicle. In a second experiment rats that were previously depleted and repleted of sodium as compared to sham depleted animals showed enhanced locomotor activity in an open field test when challenged with morphine (1 mg/kg, s.c.). These studies demonstrate that the behavioral responses induced by sodium deficiency and morphine treatment cross-sensitize with one another and suggest that common neural substrates underlie the sensitization of behaviors associated with states induced by morphine and sodium appetite.