Pretreatment with the protein kinase C activator phorbol 12,13-dibutyrate attenuates the ethanol-induced loss of the righting reflex in mice: modification by diabetes.
The effects of the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu) on the ethanol-induced loss of the righting reflex were studied in diabetic and non-diabetic mice. The ethanol-induced loss of the righting reflex was significantly less in diabetic mice than in non-diabetic mice. Intracerebroventricular (i.c.v.) pretreatment with PDBu dose- and time-dependently reduced the ethanol-induced loss of the righting reflex in non-diabetic mice. The reduction of the ethanol-induced loss of the righting reflex caused by PDBu was reversed by concomitant i.c.v. pretreatment with calphostin C, a selective PKC inhibitor. On the other hand, PDBu had no effect on the ethanol-induced loss of the righting reflex in diabetic mice. I.c.v. pretreatment with calphostin C (10 pmol) increased the ethanol-induced loss of the righting reflex in diabetic mice but not in non-diabetic mice. These results suggest that the activation of PKC reduces the ethanol-induced loss of the righting reflex in mice. Furthermore, it is possible that this attenuation of the ethanol-induced loss of the righting reflex in diabetic mice may be due in part to increased PKC activity.
Ohsawa
M
M
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Kamei
J
J
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015240:Phorbol 12,13-Dibutyrate / Q000008:administration & dosage / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism*
D002492:Central Nervous System Depressants; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D011493:Protein Kinase C