Neuroscience Letters 445 (2008) 58–61 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet The effect of intra-arterial papaverine on ECoG activity in the ketamine anesthetized rat Ayse Karatas a,∗ , Fatih Gokce b , Serif Demir b , Seyit Ankarali c a Department of Neurosurgery, Duzce University, School of Medicine, Konuralp 81620, Duzce, Turkey b Department of Physiology, Duzce University, School of Medicine, Konuralp 81620, Duzce, Turkey c Department of Physiology, Karaelmas University, School of Medicine, Kozlu 67600, Zonguldak, Turkey article info Article history: Received 14 April 2008 Received in revised form 5 August 2008 Accepted 22 August 2008 Keywords: Papaverine Epilepsy Rat Vasospasm Subarachnoid hemorrhage abstract The opium alkaloid papaverine (PPV) causes vasodilatation of the cerebral arteries through direct action on smooth muscle that reduces the constriction of smooth muscle. Intra-arterial papaverine (IAP) has been used widely to increase the regional cerebral blood flow in order to reverse the cerebral vasospasm that occurs during endovascular procedures. IAP-induced seizures have been reported, although PPV has anticonvulsive effects. This study determined the effects of IAP on electrocorticography (ECoG) in the ketamine anesthetized rats. We used 24 Sprague–Dawley male rats weighing 200–250 g. The animals were divided randomly into four groups: three treatment groups (groups 1–3) and a control (group 4). Groups 1, 2, and 3 were given 1, 7, and 14mg/kg IAP, respectively. The ECoG was compared across groups. Our results indicated that IAP did not cause seizures and that it decreased the frequency of ketamine-induced epileptiform activity in the 14mg/kg group. Crown Copyright © 2008 Published by Elsevier Ireland Ltd. All rights reserved. Papaverine (PPV) is a potent nonspecific vasodilator with many clinical uses in the treatment of arterial spasm. This drug is an opium alkaloid that dilates arteries and arterioles through direct action on smooth muscle, independent of endothelium-delivered factors. It causes arteriolar dilatation in the systemic, coronary, and cerebral circulations. The potent vasodilator effects of PPV have led to its use in the treatment of coronary graft spasm, male impo- tence, and cerebrovascular insufficiency. The use of intra-arterial papaverine (IAP) for treating symptomatic vasospasm-induced by aneurysmal subarachnoid hemorrhage (SAH) has increased [19,23]. However, the use of PPV is not without risk. Seizures are reported complication of IAP treatment, although the exact mechanism of these seizures is not known. Experimental studies have examined the effects of intraperitoneal PPV on epilepsy. The main objective of this study was to evaluate the seizure effect of IAP in rats. We examined the effects of IAP in order to more closely evaluate its use in neurosurgical practice and to eliminate any artifacts related to possible variable absorption. Abbreviations: PPV, papaverine; IAP, intra-arterial papaverine; ECoG, elec- trocorticography; SAH, subarachnoid hemorrhage; cAMP, cyclic adenosine 3 ′ ,5 ′ - monophosphate; cGMP, cyclic guanosine 3 ′ ,5 ′ -monophosphate; ms, milliseconds. ∗ Corresponding author at: Duzce Universitesi Tip Fakultesi Arastirma Hastanesi Beyin Cerrahisi Klini˘ gi, 81620 Konuralp, Duzce, Turkey. Tel.: +90 5334804412; fax: +90 3805414105. E-mail address: aysekaratas@yahoo.com (A. Karatas). This study was approved by the institutional ethics board of our medical school and was performed under institutional guide- lines for the care and use of animals in research. The study used 24 male Sprague–Dawley rats (3 months old, 200–250 g). The rats were divided randomly into four equal groups and were food-deprived for 12h before surgery. The first three groups were given different doses of PPV (1, 7, and 14mg/kg, respectively). Group 4 served as an untreated control. We chose dosages of 1 and 7mg/kg because these are close to the dosage used clinically in humans, which ranges from 100 to 780mg administered into the affected vascu- lar region [4,9,15,17,19,23,25,31]. We used 14mg/kg to determine the effects of an overdose. All of the rats were anesthetized with 100 mg/kg ketamine hydrochloride (Ketalar 50 g/ml, Eczacibasi, Istanbul, Turkey) given intraperitoneally. The left common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA) were exposed after making midline cervical ventral skin incision under an operating microscope. After electrocoagulat- ing and cutting the branches of the ECA, it was ligated and cut 1 cm distal to the CCA bifurcation. A minivascular clip was placed over the CCA, and a 0.8-mm silicone tube was inserted into the origin of the ICA, through that the ECA. After tightening a 4-0 silk suture around the ECA, the miniclip on the CCA was removed (Fig. 1). A 27-gauge syringe was connected to the silicon tube. After preparing the intra-arterial route, the rat was positioned prone on the table, with its head immobilized in a stereotaxic apparatus (David Kopf Instruments). The scalp of each rat was shaved, and using a num- ber of 15 blade, a midline skin incision was made and continued 0304-3940/$ – see front matter. Crown Copyright © 2008 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2008.08.071