Streptozotocin-induced diabetes differentially modifies haloperidol- and gamma-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 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.
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Rajkumar J
RJ
Sevak
Wouter
W
Koek
Charles P
CP
France
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D006885:Hydroxybutyrates; C111420:4-hydroxybutyric acid; D016291:Dizocilpine Maleate; D006220:Haloperidol