title: Serotonin(1A) receptor-mediated synaptic response in the rat medial prefrontal cortex is altered by early life stress: in vivo and in vitro electrophysiological studies.
abstract: Serotonin (5-HT)(1A) receptors play a critical role in the 5-HTergic mechanism associated with fear memory. Previously we showed that adult rats exposed to early postnatal stress, i.e. footshock (FS) stress experienced during the second week (PND 14-18, 2W-FS), exhibited low levels of fear expression. The present study explored whether aversive stress exposure in the second and/or the third week (PND 21-25, 3W-FS) affects the function of cortical 5-HT(1A) receptors, using in vivo and in vitro experiments. A 5-HT(1A) receptor agonist, 8-OH-DPAT (0.5 mg/kg, i.p.), slightly decreased the evoked potential in the mPFC in Non-FS control and 3W-FS group. In contrast, the evoked potential increased after 8-OH-DPAT in the 2W-FS group. The in vitro experiment using patch-clamp recording showed that application of 8-OH-DPAT (10 microM) elicited membrane hyperpolarization of pyramidal neurons in the mPFC in the Non-FS and 3W-FS groups, whereas no changes in membrane potential were observed in the 2W-FS group. These results suggest that synaptic facilitation induced by 8-OH-DPAT resulted from functional changes in cortical 5-HT(1A) receptors. Thus, aversive stress exposure during the second postnatal period appears to cause persistent changes mediated via 5-HT(1A) receptors, presumably involving signal transduction regulating the development of synaptic connectivity underlying fear circuits.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Health Sciences University of Hokkaido.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kimura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Taito
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Junko
authors.initials: J
authors.lastname: Ishida
authors.forename: Satomi
authors.initials: S
authors.lastname: Kano
authors.forename: Atsuko
authors.initials: A
authors.lastname: Ohashi
authors.forename: Shyhei
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shimamura
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000819:agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D005239:Fear / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin