Neuroscience Letters 569 (2014) 153–157 Contents lists available at ScienceDirect Neuroscience Letters jo ur nal ho me page: www.elsevier.com/locate/neulet CDP-choline attenuates scopolamine induced disruption of prepulse inhibition in rats: Involvement of central nicotinic mechanism Gulsah Uslu, Vahide Savci, Levent R. Buyukuysal, Gokhan Goktalay ∗ Department of Medical Pharmacology, Uludag University Faculty of Medicine, Bursa, Turkey h i g h l i g h t s • CDP-choline has no effect on prepulse inhibition (PPI) in naïve rats. • CDP-choline attenuated scopolamine induced PPI disruption. • Reversal effects of CDP-choline are antagonized by nicotinic antagonists mecamylamine and methyllycaconitine. a r t i c l e i n f o Article history: Received 12 February 2014 Received in revised form 24 March 2014 Accepted 27 March 2014 Keywords: CDP-choline Nicotine Prepulse Inhibition (PPI) Schizophrenia Rat(s) a b s t r a c t It has been shown that cholinergic system plays an important role in schizophrenia-associated cogni- tive 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 execu- tion 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 mech- anism in these effects was determined. CDP-choline (75, 250, 500 mg/kg) by itself had no effect on the PPI in naïve animals. Scopolamine (0.4 mg/kg; s.c.) significantly decreased the PPI levels and intraperi- toneal administration of CDP-choline (250 mg/kg) attenuated the effects of scopolamine. A non-specific nicotinic receptor antagonist, mecamylamine and an alpha 7 nicotinic receptor (7-nAChR) antagonist, methyllycaconitine were used to investigate the mechanism underlying the effects of CDP-choline. Meca- mylamine (3 mg/kg; s.c.), and methyllycaconitine (10 g; i.c.v.) completely blocked the reversal effects of CDP-choline on scopolamine induced disruption of PPI. These results demonstrate that exogenous admin- istration of CDP-choline attenuates scopolamine induced PPI disruption and show that the activation of central 7-nAChR may play a critical role in this effect. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Prepulse inhibition (PPI) is a physiological phenomenon charac- terized by the attenuation of the startle response which is caused by an intense audiogenic stimulus that is shortly (30–300 ms) pre- ceded by a weaker stimulus [16]. PPI reflects the functioning of the sensorimotor gating mechanism and healthy functioning of this mechanism is crucial for normal cognitive processes especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses [5,25,37]. Deficiency of PPI has been extensively studied in schizophrenia patients and it ∗ Corresponding author. Tel.: +90 224 295 35 67; fax: +90 224 442 81 02. E-mail addresses: goktalay@gmail.com, goktalay@uludag.edu.tr (G. Goktalay). is accepted as one of the endophenotypic factors in schizophrenia [15,17]. Several lines of evidence indicate that cholinergic system plays a crucial role in normal cognitive process and is hypothesized as an important role in schizophrenia-associated cognitive deficits [4,12]. Abnormalities in the expression and regulation of central cholinergic receptors were shown in patients with schizophre- nia [4,10,30,39]. Specifically, post-mortem binding studies have revealed that nicotinic 7 and 42, muscarinic M1, M2 and M4 subunits are mostly disturbed in schizophrenia patients. There are also genetic linkage studies implicating 7-nAChR subunit in schizophrenia [31]. Contributions of the cholinergic system to the modulation of sensorimotor gating mechanism are also well known. Cholinergic muscarinic antagonists such as scopolamine have been reported to disrupt PPI [3,21,28], and cholinergic agents http://dx.doi.org/10.1016/j.neulet.2014.03.070 0304-3940/© 2014 Elsevier Ireland Ltd. All rights reserved.