Article

Imipramine counteracts corticosterone-induced enhancement of glutamatergic transmission and impairment of long-term potentiation in the rat frontal cortex

Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
Pharmacological reports: PR (Impact Factor: 1.93). 11/2011; 63(6):1404-12. DOI: 10.1016/S1734-1140(11)70704-6
Source: PubMed

ABSTRACT

The effects of corticosterone administration lasting for 7 and 21 days were studied ex vivo in rat frontal cortex slices prepared 48 h after the last dose of the hormone. In slices originating from corticosterone-treated animals, the amplitude of extracellular field potentials recorded in cortical layer II/III was increased. Corticosterone administration also resulted in an increase of the mean frequency, but not the mean amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in layer II/III pyramidal neurons. These effects were accompanied by a reduced magnitude of long-term potentiation (LTP) of field potentials. In a separate set of experiments, rats were treated with corticosterone for 21 days and additionally with a tricyclic antidepressant, imipramine, beginning on the eighth day of corticosterone administration. In this experimental group, the amplitude of field potentials, the mean frequency of sEPSCs and the magnitude of LTP were not different from the control, indicating that corticosterone-induced modifications of basal glutamatergic transmission and synaptic plasticity were reversed by the antidepressant.

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    • "It has been demonstrated that the level of spontaneous glutamate release adjusts the plasticity threshold at single synapses, thus representing a form of metaplasticity[23]. In line with these results, our previous study demonstrated that repeated corticosterone administration-induced enhancement of spontaneous excitatory transmission coincides with a reduced possibility for LTP induction in the rat motor cortex[4]. Of note, blockade of the NMDA component of spontaneous EPSCs has been implicated in a rapid antidepressant-like effect of ketamine and other NMDA receptor antagonists in animal models[2]. "
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