Diazepam inhibits the induction and maintenance of LTP of C-fiber evoked field potentials in spinal dorsal horn of rats

The benzodiazepine diazepam impairs memory and long-term potentiation (LTP) in the hippocampus. Here, we investigate the effect of diazepam on LTP of C-fiber evoked field potentials in spinal dorsal horn, which is relevant to pathological pain. LTP of C-fiber evoked field potentials was recorded in the superficial layers of spinal dorsal horn in urethane-anesthetized Sprague--Dawley rats. Diazepam was applied locally at the recording spinal segments before and after LTP induction by tetanic stimulation. We found (1) Diazepam completely blocked LTP induction. (2) Diazepam and midazolam reversed spinal LTP, when applied at 30 min after LTP induction and depressed but could not reverse spinal LTP, when applied at 3 h after LTP induction. (3) Pretreatment with benzodiazepine receptor antagonist flumazenil or GABA(A) receptor antagonist bicuculline completely blocked the inhibitory effects of diazepam on spinal LTP. In contrast, when the inhibitory effect of diazepam was fully established, neither of these antagonists was capable of reversing the inhibition by diazepam. (4) Spinal application of the GABA(A) receptor agonist 3-amino-1-propanesulfonic acid (3-APSA) at a dose of 50 microg, produced a transient inhibition of spinal LTP. These results suggest that diazepam might prevent and depress spinal plastic change produced by noxious stimulation via activation of the GABA(A) -benzodiazepine receptor complex.