CDP-choline attenuates scopolamine induced disruption of prepulse inhibition in rats: involvement of central nicotinic mechanism.
It has been shown that cholinergic system plays an important role in schizophrenia-associated cognitive deficits, therefore cholinergic drugs are novel targets for the treatment of cognitive deficits seen in schizophrenia. We aimed to test the effects of CDP-choline on sensorimotor gating functioning, which is an important function for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. In this study, prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning, and the effects of CDP-choline on scopolamine induced PPI disruption were evaluated in rats. Furthermore, the contribution of the cholinergic mechanism in these effects was determined. CDP-choline (75, 250, 500mg/kg) by itself had no effect on the PPI in naïve animals. Scopolamine (0.4mg/kg; s.c.) significantly decreased the PPI levels and intraperitoneal administration of CDP-choline (250mg/kg) attenuated the effects of scopolamine. A non-specific nicotinic receptor antagonist, mecamylamine and an alpha 7 nicotinic receptor (α7-nAChR) antagonist, methyllycaconitine were used to investigate the mechanism underlying the effects of CDP-choline. Mecamylamine (3mg/kg; s.c.), and methyllycaconitine (10μg; i.c.v.) completely blocked the reversal effects of CDP-choline on scopolamine induced disruption of PPI. These results demonstrate that exogenous administration of CDP-choline attenuates scopolamine induced PPI disruption and show that the activation of central α7-nAChR may play a critical role in this effect.
Department of Medical Pharmacology, Uludag University Faculty of Medicine, Bursa, Turkey.
Gulsah
G
Uslu
Department of Medical Pharmacology, Uludag University Faculty of Medicine, Bursa, Turkey.
Vahide
V
Savci
Department of Medical Pharmacology, Uludag University Faculty of Medicine, Bursa, Turkey.
Levent R
LR
Buyukuysal
Department of Medical Pharmacology, Uludag University Faculty of Medicine, Bursa, Turkey. Electronic address: goktalay@gmail.com.
Gokhan
G
Goktalay
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000161:Acoustic Stimulation; D000818:Animals; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D065808:Prepulse Inhibition / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018733:Nicotinic Antagonists; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D003566:Cytidine Diphosphate Choline; D008464:Mecamylamine; D012601:Scopolamine; D000157:Aconitine
CDP-choline; Nicotine; Prepulse Inhibition (PPI); Rat(s); Schizophrenia