title: Direct alteration of a specific inhibitory circuit of the hippocampus by antidepressants.
abstract: Correct brain functioning relies on the precise activity of a myriad of synapses assembling neurons in complex networks. In the hippocampus, highly diverse inhibitory circuits differently govern several physiologically relevant network activities. Particularly, perisomatic inhibition provided by specific interneurons was proposed to control emotional states, and could therefore be affected by mood disorders and their therapy. We found that both chronic and acute administration of two major antidepressants, imipramine and fluoxetine, strongly and directly altered GABA-mediated (GABAergic) hippocampal neurotransmission in mice and rats, independently of their effects on amine reuptake systems. These drugs affected GABA release from synapses formed by fast-spiking cells, but not interneurons expressing cannabinoid receptor type 1, resulting in the disruption of γ oscillations. This differential effect, shared by two types of antidepressants, suggests a new mechanism of action of these medications, and a possible role of perisomatic inhibition in depressive disorders.
authors.affiliation: European Brain Research Institute, 00143 Rome, Italy.
authors.forename: Pablo
authors.initials: P
authors.lastname: Méndez
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazienti
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabó
authors.forename: Alberto
authors.initials: A
authors.lastname: Bacci
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003627:Data Interpretation, Statistical; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007099:Imipramine / Q000494:pharmacology; D007266:Inhibition, Psychological; D007395:Interneurons / Q000187:drug effects; D008297:Male; D009415:Nerve Net / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D015306:Biogenic Monoamines; D005473:Fluoxetine; D007099:Imipramine; D043884:Receptor, Cannabinoid, CB1; D017367:Selective Serotonin Reuptake Inhibitors; D005680:gamma-Aminobutyric Acid