title: Contribution of serotonin type 3 receptors in the successful extinction of cued or contextual fear conditioned responses: interactions with GABAergic signaling.
abstract: The changes in serotonin type 3 (5-HT) receptor activity influence memory and emotional regulation,the two essential components underlying the successful extinction of conditioned fear. These studies determined if blocking 5-HT3 receptors with granisetron influences the extinction of fear in male Sprague-Dawley rats. In Experiment 1, preextinction granisetron (0.5 or 1.0 mg/kg intraperitoneally) d~d not affect cued extinction learning but enhanced memory for the extinction session on retention test given 24 and 48 h later. In Experiment 2, granisetron injections given on days 1 and 4 during 6 days of extinction training reduced fear produced by contextual fear conditioning. Experiments 3 and 4 examined if 5-HT3 antagonists influence extinction memory by interactions with y-aminobutyric acid (GABA). The expression of the GABA receptor clustering protein gephyrin was significantly A elevated in the amygdala after cued fear extinction training and a subsequent extinction retention test given 24 h later. Gephyrin expression in the hippocampus but not in the amygdala or the medial prefrontal cortex was significantly reduced after contextual fear extinction sessions given 1 or 5 days after training. The current studies reveal the beneficial effects of 5-HT3 receptor activity in improving new learning associated with extinction of fearful memories and suggest that these actions could be mediated through influences on central GABAergic systems.
authors.affiliation: Department of Psychology, University of Virginia, Charlottesville, VA 22904, USA.
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Cedric L
authors.initials: CL
authors.lastname: Williams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017829:Granisetron / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D017829:Granisetron; D008565:Membrane Proteins; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C073441:gephyrin