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.
Sevak
Rajkumar J
RJ
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Koek
Wouter
W
France
Charles P
CP
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