Gabapentin prevents cortical spreading depolarization-induced disinhibition

• Published in: Neuroscience 2017-10, Vol.361, p.1-5
• Main Authors: Mesgari, Masoud, Krüger, Johanna, Riemer, Christopher Theo, Khaleghi Ghadiri, Maryam, Kovac, Stjepana, Gorji, Ali
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Amines - pharmacology; Animals; anticonvulsive; Cortical Spreading Depression - drug effects; Cyclohexanecarboxylic Acids - pharmacology; Disease Models, Animal; epilepsy; gamma-Aminobutyric Acid - pharmacology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Neocortex - drug effects; Neocortex - physiopathology; Neurons - drug effects; Neurons - physiology; Rats, Wistar; seizure; spreading depolarization; stroke
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2017.08.009

•Spreading depolarization (SD) plays an important role in migraine and epilepsy.•Gabapentin (GBP) is widely used for the treatment of epilepsy and migraine.•GBP enhanced evoked inhibitory post synaptic potentials after induction of SD.•GBP inhibited long-term potentiation of synaptic transmission after induction of SD.•GBP modulates synaptic properties and GABAergic function after induction of SD. Cortical spreading depolarization (CSD) has an important role in brain diseases such as stroke, subarachnoid hemorrhage, migraine with aura, and epilepsy. Several anti-epileptic drugs (AEDs) are used to treat paroxysmal brain diseases and are thus known to suppress CSD. One of these AEDs is gabapentin (GBP) which has been traditionally used for treatment of some CSD-related neurological diseases. We applied intra- and extracellular recordings to investigate the effect of CSD on inhibitory post synaptic potentials (IPSPs) and synaptic properties of rodent neocortex after application of GBP. Application of GBP after CSD increased the amplitude of IPSPs. In addition, GBP inhibited induction of long-term potentiation after CSD. These data support an effect of GBP on GABA-mediated inhibition in the late hyperexcitable phase of CSD. Modulations of synaptic properties and post-CSD GABAergic function are likely GBP’s mechanisms of action in CSD-related disorders. These mechanisms could be targeted for further drug discovery in CSD-related diseases.