Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs
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Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs. / Abrams, J K; Johnson, P L; Hay-Schmidt, Anders; Mikkelsen, J D; Shekhar, A; Lowry, C A.
In: Neuroscience, Vol. 133, No. 4, 2005, p. 983-97.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Serotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs
AU - Abrams, J K
AU - Johnson, P L
AU - Hay-Schmidt, Anders
AU - Mikkelsen, J D
AU - Shekhar, A
AU - Lowry, C A
PY - 2005
Y1 - 2005
N2 - Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.
AB - Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state. In addition, these anxiogenic drugs, excluding yohimbine, had convergent actions on an anatomically-defined subset of serotonergic neurons within the middle and caudal, dorsal subdivision of the DR. High resolution topographical analysis revealed that at the mid-rostrocaudal level, caffeine and FG-7142 had convergent effects on c-Fos expression in serotonergic neurons that were restricted to a previously undefined region, which we have named the shell region of the dorsal part of the dorsal raphe nucleus (DRDSh), that overlaps the anatomical border between the dorsal part of the dorsal raphe nucleus, the ventral part of the dorsal raphe nucleus (DRV), and the ventrolateral part of the dorsal raphe nucleus (DRVL). Retrograde tracing methods revealed that DRDSh contains large numbers of neurons projecting to the basolateral amygdaloid nucleus, a forebrain structure important for emotional appraisal and modulation of anxiety-related physiological and behavioral responses. Together these findings support the hypothesis that there is a functional topographical organization in the DR and are consistent with the hypothesis that anxiogenic drugs have selective actions on a subpopulation of serotonergic neurons projecting to a distributed central autonomic and emotional motor control system regulating anxiety states and anxiety-related physiological and behavioral responses.
KW - Adrenergic alpha-Antagonists
KW - Analysis of Variance
KW - Animals
KW - Anti-Anxiety Agents
KW - Arousal
KW - Behavior, Animal
KW - Blotting, Western
KW - Brain
KW - Brain Mapping
KW - Caffeine
KW - Carbolines
KW - Cell Count
KW - Central Nervous System Stimulants
KW - Feeding Behavior
KW - GABA Antagonists
KW - Gene Expression Regulation
KW - Immunohistochemistry
KW - Male
KW - Neural Pathways
KW - Neurons
KW - Piperazines
KW - Proto-Oncogene Proteins c-fos
KW - Raphe Nuclei
KW - Rats
KW - Rats, Wistar
KW - Serotonin
KW - Serotonin Receptor Agonists
KW - Stilbamidines
KW - Time Factors
KW - Tryptophan Hydroxylase
KW - Video Recording
KW - Yohimbine
U2 - 10.1016/j.neuroscience.2005.03.025
DO - 10.1016/j.neuroscience.2005.03.025
M3 - Journal article
C2 - 15916857
VL - 133
SP - 983
EP - 997
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 4
ER -
ID: 47928621