The activation of Translocator protein (18 kDa) (TSPO) has been demonstrated to mediate rapid anxiolytic efficacy in\nstress response and stress-related disorders. This protein is involved in the synthesis of endogenous neurosteroids\nthat promote ?-aminobutyric acid (GABA)-mediated neurotransmission in the central neural system. However, little\nis known about the functions and the underlying mechanisms of TSPO in chronic pain-induced anxiety-like behaviors.\nThe novel TSPO ligand N-benzyl-N-ethyl-2-(7,8-dihydro-7-benzyl-8-oxo-2-phenyl-9H-purin-9-yl) acetamide (ZBD-2) was\nused in the present study. We found that ZBD-2 (0.15 or 1.5 mg/kg) significantly attenuated anxiety-like behaviors in\nmice with chronic inflammatory pain induced by hindpaw injection of complete Freund�s adjuvant (CFA). However, the\ntreatment did not alter the nociceptive threshold or inflammation in the hindpaw. Hindpaw injection of CFA induced\nthe upregulation of TSPO, GluR1-containing ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors,\nand NR2B-containing N-methyl-D-aspartate (NMDA) receptors in the basolateral amygdala (BLA). ZBD-2 administration\nreversed the alterations of the abovementioned proteins in the BLA of the CFA-injected mice. Electrophysiological\nrecording revealed that ZBD-2 could prevent an imbalance between excitatory and inhibitory transmissions in the\nBLA synapses of CFA-injected mice. Therefore, as the novel ligand of TSPO, ZBD-2 induced anxiolytic effects, but did\nnot affect the nociceptive threshold of mice under chronic pain. The anxiolytic effects of ZBD-2 were related to the\nregulation of the balance between excitatory and inhibitory transmissions in the BLA.
Loading....