Streptozotocin-induced diabetes differentially modifies haloperidol- and γ-hydroxybutyric acid (GHB)-induced catalepsy

To examine whether dopamine-mediated behavioral effects are altered in diabetes, this study compared the cataleptic effects of the dopamine receptor antagonist haloperidol (0.032-0.56 mg/kg) and γ-hydroxybutyric acid (GHB; 56-1000 mg/kg) in control and streptozotocin (STZ)-treated rats. Haloperidol and GHB produced catalepsy in control and diabetic rats; haloperidol was less potent in diabetic rats (D₅₀ = 0.44 mg/kg) than in controls (D ₅₀ = 0.19 mg/kg), while GHB was more potent in diabetic rats (D ₅₀ = 392 mg/kg) than in controls (D₅₀ = 550 mg/kg). In diabetic rats, the non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist dizocilpine (0.32 mg/kg) further attenuated haloperidol-induced catalepsy (D₅₀ = 1.2 mg/kg) and further enhanced GHB-induced catalepsy (D₅₀ = 248 mg/kg). That haloperidol is less potent to produce catalepsy in diabetic rats is consistent with reports of altered dopamine receptor binding in diabetes.