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

Sevak RJ, Koek W, France CP

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

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 gamma-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 (D(50)=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 (D(50)=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 (D(50)=1.2 mg/kg) and further enhanced GHB-induced catalepsy (D(50)=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.

Published 4 July 2005 in Eur J Pharmacol, 517(1): 64-7.
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