title: Altered neuropeptide Y and neurokinin messenger RNA expression and receptor binding in stress-sensitised rats.
abstract: A single session of footshocks in rats causes long-lasting sensitisation of behavioural, hormonal and autonomic responses to subsequent novel stressful challenges as well as altered pain sensitivity. These changes mimic aspects of post-traumatic stress disorder in humans. Our aim was to identify neuropeptide substrates in the central nervous system involved in stress sensitisation. Male Wistar rats were exposed to ten footshocks in 15 min (preshocked) or placed in the same cage without shocks (control). Two weeks later, rats were placed in a novel cage, subjected to 5 min of 85 dB noise, and returned to their home cage. Rats were killed either before or 1 h after noise and their brains processed for in situ hybridization for neuropeptide Y (NPY) and beta-preprotachykinin-I (PPT) mRNA. Additional groups of rats were killed under basal conditions and brains processed for NPY and neurokinin receptor binding with radiolabelled ligands. Two weeks after footshock treatment NPY mRNA expression was increased in the basolateral amygdala and showed preshockxnoise interaction in the locus coeruleus (down after noise in controls, lower basal and unchanged after noise in preshocked). PPT expression in the lateral parabrachial nucleus also showed preshockxnoise interaction (up after noise in controls, higher basal and down after noise in preshocked), and was increased after noise in the periaquaeductal grey. NK1 receptor binding in the agranular insular cortex and arcuate nucleus of the hypothalamus and NK2 receptor binding in the amygdala was lower in preshocked rats than in controls. Altered expression of NPY in the basolateral amygdala and locus coeruleus could contribute to or compensate for behavioural and autonomic sensitisation in preshocked rats. Altered PPT expression in the parabrachial nucleus may be involved in the altered pain processing seen in this model. Lower NK1 and NK2 receptor numbers in cortex, hypothalamus and amygdala may reflect secondary adaptations to altered neuropeptide release. These long-term changes in brain neuropeptide systems could offer novel leads for pharmacological modulation of long-term stress-induced sensitisation.
authors.affiliation: Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, P.O. box 80040, 3508 TA Utrecht, The Netherlands.
authors.forename: Robert P J
authors.initials: RP
authors.lastname: de Lange
authors.forename: Victor M
authors.initials: VM
authors.lastname: Wiegant
authors.forename: Rianne
authors.initials: R
authors.lastname: Stam
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D001522:Behavior, Animal; D004597:Electroshock / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology*; D046353:Immobility Response, Tonic; D008124:Locomotion / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D011485:Protein Binding / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015320:Tachykinins / Q000235:genetics*
chemical_list: D009478:Neuropeptide Y; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D017476:Receptors, Neuropeptide Y; D015320:Tachykinins; C044206:preprotachykinin