Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a gene–environment rat model of depression

• Published in: The international journal of neuropsychopharmacology Vol. 12; no. 4; pp. 553 - 559
• Main Authors: Ryan, Ben, Musazzi, Laura, Mallei, Alessandra, Tardito, Daniela, Gruber, Suzanne H. M., El Khoury, Aram, Anwyl, Roger, Racagni, Giorgio, Mathé, Aleksander A., Rowan, Michael J., Popoli, Maurizio
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.05.2009; Oxford University Press
• Subjects: Animals; Blotting, Western; Depression - genetics; Depression - pathology; Depression - psychology; Electric Stimulation; Electrophysiology; Environment; Excitatory Postsynaptic Potentials - drug effects; Long-Term Potentiation - physiology; Male; Medicin och hälsovetenskap; Neuronal Plasticity - physiology; Rats; Receptors, Glutamate - drug effects; Receptors, Glutamate - genetics; Receptors, N-Methyl-D-Aspartate - physiology; Stress, Psychological - pathology; Stress, Psychological - psychology; Synapses - physiology; Synaptosomes - physiology; stress; Depression; synaptic plasticity; NMDA receptor; gene–environment
• ISSN: 1461-1457; 1469-5111; 1469-5111
• DOI: 10.1017/S1461145708009607

An animal model of depression combining genetic vulnerability and early-life stress (ELS) was prepared by submitting the Flinders Sensitive Line (FSL) rats to a standard paradigm of maternal separation. We analysed hippocampal synaptic transmission and plasticity in vivo and ionotropic receptors for glutamate in FSL rats, in their controls Flinders Resistant Line (FRL) rats, and in both lines subjected to ELS. A strong inhibition of long-term potentiation (LTP) and lower synaptic expression of NR1 subunit of the NMDA receptor were found in FSL rats. Remarkably, ELS induced a remodelling of synaptic plasticity only in FSL rats, reducing inhibition of LTP; this was accompanied by marked increase of synaptic NR1 subunit and GluR2/3 subunits of AMPA receptors. Chronic treatment with escitalopram inhibited LTP in FRL rats, but this effect was attenuated by prior ELS. The present results suggest that early gene–environment interactions cause lifelong synaptic changes affecting functional and molecular aspects of plasticity, partly reversed by antidepressant treatments.