title: Analysis of extinction acquisition to attenuated tones in prenatally stressed and non-stressed offspring following auditory fear conditioning.
abstract: Stimulus generalization occurs when stimuli with characteristics similar to a previously conditioned stimulus (CS) become able to evoke a previously conditioned response. Experimental data (Lissek et al., 2005) indicate that patients with post-traumatic stress disorder (PTSD), more often show stimulus generalization following fear conditioning when tested under laboratory conditions. Factors surrounding this observation may contribute to two common features of PTSD: 1) hyper-responsiveness to sensory stimuli reminiscent of those associated with the original trauma, and 2) resistance of PTSD to extinction-based therapies. Adverse early experience is considered a risk factor for the later development of PTSD and in the present experiments we hypothesized that stimulus generalization would occur in an animal model of adverse early experience, the prenatally stressed (PS) rat. Adult PS and control (CON) rats underwent extensive pre-habituation to a conditioning chamber followed by conventional auditory fear conditioning. The next day both groups began an extinction regimen where a series of quieter (attenuated), CSs were administered prior to the full 75 dB training CS. When tested in this manner, PS rats froze at significantly lower tone amplitudes than did CON offspring on the first day of extinction training. This suggests that the PS rats had stimulus-generalized the CS to lower decibel tones. In addition to this finding, we also observed that PS rats froze more often and longer during three ensuing days of extinction training to attenuated tones. Group differences vanished when PS and CON rats were extinguished under conventional conditions. Thus, it appears that the two extinction regimens differed in their aversive cue saliency for the PS vs. CON rats. Follow-up prefrontal cortex transcriptome probing suggests that cholinergic and dopaminergic alterations may be involved.
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26506-9128 USA. Electronic address: asalm@hsc.wvu.edu.
authors.forename: A K
authors.initials: AK
authors.lastname: Salm
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26506-9128 USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Lally
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26506-9128 USA; Life Sciences, The University of Manchester, Carys Bannister Building, Dover St, Manchester M13 9PL, UK.
authors.forename: E
authors.initials: E
authors.lastname: Borysiewicz
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26506-9128 USA.
authors.forename: D
authors.initials: D
authors.lastname: Fil
authors.affiliation: Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, WV 26506-9128 USA.
authors.forename: G
authors.initials: G
authors.lastname: Konat
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D002540:Cerebral Cortex / Q000503:physiopathology; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D046352:Freezing Reaction, Cataleptic; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D018377:Neurotransmitter Agents
keywords: Auditory processing; Cue saliency; PTSD; Prefrontal gene expression; Prenatal stress; Sensory hyperresponsivity; Stimulus generalization