title: Effects of single and simultaneous lesions of serotonergic and noradrenergic pathways on open-space and bright-space anxiety-like behavior in two animal models.
abstract: The objective of the present study is to investigate the effects of single and simultaneous lesions of the noradrenergic and serotonergic pathways (NA-X, 5-HT-X and XX, respectively) by intracerebroventricular administration of selective neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-HCl (DSP-4) and 5,7-dihydroxytryptamine (5,7-DHT) on anxiety-like behavior in rats. To evaluate the effects of the various lesions, animals were tested in elevated plus-maze (EPM) and light-dark (LD) paradigms. In EPM, single lesions produced strong, statistically significant increase (p<0.001) of both time spent in the open arms (OT) and number of entries into the open arms (OE) compared to sham-lesioned animals. Simultaneous lesion further strengthened this anxiolytic effect causing an approximate 500% elevation of OT compared to sham-lesioned animals. In LD, 5-HT lesion caused a significant (p<0.05) increase in both light movement time and light horizontal activity parameters compared to intact, sham, and NA-lesioned groups. Neither of the lesions caused any change in the spontaneous locomotor activity of the animals up to 15min as measured in activity meter. These findings suggest that single and simultaneous lesions of 5-HT- and NA-pathways modify anxiety-related state of experimental animals to different extents and these modifications alter the behavior of animals differently in the two models used: NA-X and 5-HT-X reduce open space anxiety-like behavior and XX further strengthens this effect in the EPM, while only 5-HT-X is resulting in reduced bright-space anxiety-like behavior leaving the performance of NA-X and XX animals unchanged.
authors.affiliation: Division of Preclinical Research, EGIS Pharmaceuticals Plc., Bökényföldi út 116, Budapest H-1165, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Sziray
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Kuki
authors.forename: Katalin M
authors.initials: KM
authors.lastname: Nagy
authors.forename: Bernadett
authors.initials: B
authors.lastname: Markó
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Kompagne
authors.forename: György
authors.initials: G
authors.lastname: Lévay
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000009:adverse effects / Q000494:pharmacology; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D018663:Adrenergic Agents / Q000009:adverse effects / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000209:etiology*; D001596:Benzylamines / Q000009:adverse effects / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000009:adverse effects / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D015116:5,7-Dihydroxytryptamine; D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D001596:Benzylamines; D003891:Desipramine; D005473:Fluoxetine; D009638:Norepinephrine; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; C012102:DSP 4