Gabapentin — Actions on adult superficial dorsal horn neurons

• Published in: Neuropharmacology Vol. 43; no. 7; pp. 1077 - 1081
• Main Authors: Moore, K.A, Baba, H, Woolf, C.J
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2002; Elsevier
• Subjects: Acetates - pharmacology; Amines; Animals; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Cyclohexanecarboxylic Acids; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Gabapentin; gamma-Aminobutyric Acid; In Vitro Techniques; Male; Medical sciences; N-Methylaspartate - pharmacology; Neuropharmacology; NMDA; Pharmacology. Drug treatments; Posterior Horn Cells - drug effects; Posterior Horn Cells - physiology; Rats; Rats, Sprague-Dawley; Spinal cord; Synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; NMDA; Spinal cord; Gabapentin; Synaptic transmission; Rat; Rodentia; Central nervous system; Anticonvulsant; Posterior spinal horn; In vitro; Biological activity; Vertebrata; Mammalia; Animal; Mechanism of action; Gabaergic receptor B
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00226-5

Despite identification of GABA B receptors with gb1a-gb2 composition and the α2δ calcium channel subunit as putative molecular targets for gabapentin (GBP), its cellular mechanism of action has remained elusive. Therefore, we have used an in vitro spinal cord slice preparation to study the effects of GBP on lamina II neurons. The frequency and amplitude of spontaneous EPSCs and IPSCs were unaffected by GBP, suggesting presynaptic neurotransmitter release is not regulated. Direct modulation of postsynaptic membrane excitability is also unlikely since the level of holding current required to maintain neurons at −70, 0 and +45 mV was unaffected by GBP. Effects on excitatory and inhibitory synaptic transmission were variable across the population. Primary afferent-evoked fast glutamatergic EPSCs were unaffected by GBP, while evoked NMDA receptor-mediated EPSCs and IPSCs were variably affected. In contrast, GBP enhanced responses to bath applied NMDA in 71% of neurons. Thus, in adult rat dorsal horn, synaptic and extrasynaptic NMDA receptors may be differentially regulated by GBP perhaps due to differences in subunit composition.