Repeated administration of imipramine attenuates glutamatergic transmission in rat frontal cortex.
The effects of repeated administration of a tricyclic antidepressant, imipramine, lasting 14 days (10 mg/kg p.o., twice daily), were studied ex vivo in rat frontal cortex slices prepared 48 h after last dose of the drug. In slices prepared from imipramine-treated animals the mean frequency, and to a lesser degree the mean amplitude, of spontaneous excitatory postsynaptic currents recorded from layer II/III pyramidal neurons, were decreased. These effects were accompanied by a reduction of the initial slope ratio of pharmacologically isolated N-methyl-D-aspartate to AMPA/kainate receptor-mediated stimulation-evoked excitatory postsynaptic currents. Imipramine treatment also resulted in a decrease of extracellular field potentials evoked in layer II/III by stimulation of underlying sites in layer V. These results indicate that chronic treatment with imipramine results in an attenuation of the release of glutamate and an alteration in the postsynaptic reactivity of ionotropic glutamate receptors in rat cerebral cortex.
Tokarski
K
K
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Bobula
B
B
Wabno
J
J
Hess
G
G
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007099:Imipramine