Neuroscience Letters 578 (2014) 39–43 Contents lists available at ScienceDirect Neuroscience Letters jo ur nal ho me page: www.elsevier.com/locate/neulet Plasma glucocorticoids differentially modulate phasic and tonic GABA inhibition during early postnatal development in rat spinal lamina II Vivien Zell a,b , Ulrike Hanesch b , Pierrick Poisbeau a , Fernand Anton b , Pascal Darbon a,∗ a Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 5 rue Blaise Pascal, F-67084 Strasbourg, France b Laboratory of Neurophysiology and Psychobiology, University of Luxembourg, 162A, avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg h i g h l i g h t s • Plasma CORT regulates phasic but not tonic GABA spinal inhibition. • Hypercortisolemic rats display enhanced phasic GABA inhibition during development. • Rat with high plasma CORT level exhibited reduced mechanical pain sensitivity. • Extrasynaptic GABA current increases during the first postnatal weeks. a r t i c l e i n f o Article history: Received 28 April 2014 Received in revised form 5 June 2014 Accepted 10 June 2014 Available online 23 June 2014 Keywords: Glucocorticoids Spinal dorsal horn GABA synaptic transmission GABA extrasynaptic transmission Mechanical pain sensitivity a b s t r a c t Nociceptive processing is tuned by GABA A receptor-mediated inhibition in the spinal cord dorsal horn that undergoes postnatal maturation in rodents. These GABAergic inhibitory postsynaptic currents (IPSCs) are modulated by 35-reduced steroids during early postnatal development in spinal cord lamina II. Thus an enhanced phasic inhibition is present in neonates and decreases over time. GABA can also activate extrasynaptic receptors, giving rise to tonic inhibition. In this study, we characterized the con- tribution of plasma corticosterone (CORT) to postnatal maturation of spinal phasic and, for the first time, tonic GABAergic inhibitions. We used Fisher and Lewis rat strains displaying respectively high and low hypothalamic-pituitary-adrenal axis reactivity, compared to control Sprague-Dawley rats. Mea- sured plasma CORT levels were significantly higher in Fisher rats, which also displayed significantly higher mechanical nociceptive thresholds, supporting the hypothesis of an antinociceptive action of CORT. Recorded GABA A IPSCs shortened during maturation in all strains while remaining larger in Fisher rats. Blocking the 5-reduction of steroids in Fisher rats produced a further decrease of IPSC deactivation time constant. In contrast, GABA A tonic inhibition progressively increased during maturation, without any difference among strains. In conclusion, we show that both phasic and tonic GABAergic inhibitions undergo postnatal maturation in lamina II. Moreover spinal production of 35-reduced steroids that presumably derive from plasma CORT is correlated to spinal GABA A phasic (but not tonic) inhibition and to mechanical nociceptive thresholds. © 2014 Elsevier Ireland Ltd. All rights reserved. In rodents, inhibition in the dorsal spinal cord plays a major role in sensory information processing. In spinal superficial Abbreviations: 35NS, 35-reduced neurosteroids; ACSF, artificial cere- brospinal fluid; BIC, bicuculline; CORT, corticosterone; FIN, finasteride; GABA A R, GABA A receptor; FIS, Fischer; GABA, -aminobutyric acid; GBZ, gabazine; GC, gluco- corticoids; HPA, hypothalamic-pituitary-adrenal axis; IPSC, inhibitory postsynaptic current; LEW, Lewis; PX, X postnatal day; RIA, radioimmunoassay; SD, Sprague- Dawley; SHRP, stress hyporesponsive period. ∗ Corresponding author. Tel.: +33 368851443. E-mail addresses: pdarbon@inci-cnrs.unistra.fr, pascal.darbon@unistra.fr (P. Darbon). laminae, fast inhibitory synaptic transmission is mediated by both glycine and GABA A receptors (GABA A R) [1]. GABA A phasic inhi- bition mediated by synaptic receptors is high at birth and then progressively decreases during early postnatal development [2]. Besides, it has been shown that enhanced inhibitory transmis- sion prevents or alleviates hyperalgesia and allodynia [3,4]. Apart from phasic inhibition, a tonic GABAergic inhibition mediated by extrasynaptic GABA A R has also been reported [5]. Both types of GABA inhibitions have different spatiotemporal resolutions. Due to its properties, the tonic inhibition acts as a major fil- ter, which reduces neuronal network excitability [6]. However, to our knowledge little is known regarding the early postnatal http://dx.doi.org/10.1016/j.neulet.2014.06.035 0304-3940/© 2014 Elsevier Ireland Ltd. All rights reserved.