lasma glucocorticoids differentially modulate phasic and tonic GABA nhibition during early postnatal development in rat spinal lamina II

Nociceptive processing is tuned by GABAA 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 contribution 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. Measured 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 GABAA 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, GABAA 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 GABAA phasic (but not tonic) inhibition and to mechanical nociceptive thresholds. Please cite this article in press as: V. Zell, et al., Plasma glucocorticoids early postnatal development in rat spinal lamina II, Neurosci. Lett. (20 n rodents, inhibition in the dorsal spinal cord plays a major ole in sensory information processing. In spinal superficial Abbreviations: 3 5 NS, 3 5 -reduced neurosteroids; ACSF, artificial cererospinal fluid; BIC, bicuculline; CORT, corticosterone; FIN, finasteride; GABAAR, ABAA receptor; FIS, Fischer; GABA, -aminobutyric acid; GBZ, gabazine; GC, glucoorticoids; HPA, hypothalamic-pituitary-adrenal axis; IPSC, inhibitory postsynaptic urrent; LEW, Lewis; PX, X postnatal day; RIA, radioimmunoassay; SD, Spragueawley; SHRP, stress hyporesponsive period. ∗ Corresponding author. Tel.: +33 368851443. E-mail addresses: pdarbon@inci-cnrs.unistra.fr, pascal.darbon@unistra.fr P. Darbon). ttp://dx.doi. org/10.1016/j.neulet. 2014.06. 035 304-3940/© 2014 Published by Elsevier Ireland Ltd. 32 33 34 35 36 37 38 39 © 2014 Published by Elsevier Ireland Ltd. laminae, fast inhibitory synaptic transmission is mediated by both glycine and GABAA receptors (GABAAR) [1]. GABAA phasic inhibition 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 transmission prevents or alleviates hyperalgesia and allodynia [3,4]. Apart from phasic inhibition, a tonic GABAergic inhibition mediated by extrasynaptic GABAAR has also been reported [5]. Both types differentially modulate phasic and tonic GABA inhibition during 14), http://dx.doi. org/10.1016/j.neulet. 2014.06. 035 of GABA inhibitions have different spatiotemporal resolutions. Due to its properties, the tonic inhibition acts as a major filter, which reduces neuronal network excitability [6]. However, to our knowledge little is known regarding the early postnatal 40 41 42 43