Swim stress activates serotonergic and nonserotonergic neurons in specific subdivisions of the rat dorsal raphe nucleus in a temperature-dependent manner

• Published in: Neuroscience Vol. 197; pp. 251 - 268
• Main Authors: Kelly, K.J, Donner, N.C, Hale, M.W, Lowry, C.A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-12-2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Body Temperature Regulation - physiology; c-Fos; Cell Count; dorsal raphe nucleus; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; lateral parabrachial nucleus; Male; Neurology; Neurons - physiology; Raphe Nuclei - physiopathology; raphe pallidus; Rats; Rats, Wistar; Serotonergic Neurons - physiology; serotonin; spinoparabrachial; Stress, Psychological - physiopathology; Swimming; Temperature; Tryptophan Hydroxylase - metabolism; Vertebrates: nervous system and sense organs; median raphe nucleus; least significant difference; lateral parabrachial nucleus, dorsal part; serotonin receptor, 1B subtype; DRV; DRVL/VLPAG; spinoparabrachial; phosphate-buffered saline; phosphate-buffered saline with 0.1% Triton X-100; MPO; DR; Tb; 8-OH-DPAT; serotonin; home cage; LSD; PBS; raphe pallidus nucleus; swim stress; dorsal raphe nucleus, caudal part; dorsal raphe nucleus, dorsal part; medial preoptic area; dorsal raphe nucleus, interfascicular part; IBAT; dorsal raphe nucleus; MnR; LPBel; 5-hydroxyindoleacetic acid; dorsal raphe nucleus, ventral part; 5-HT 1B; 5-HT 1A; dorsomedial hypothalamus; LPB; core body temperature; TPH2; serotonin receptor, 1A subtype; TPH1; interscapular brown adipose tissue; tryptophan hydroxylase 2; LPBd; tryptophan hydroxylase 1; c-Fos; lateral parabrachial nucleus; TPH; analysis of variance; ANOVA; dorsal hypothalamic area; tryptophan hydroxylase; 5-HT 2A; DMH; SS; dorsal raphe nucleus, ventrolateral part/ventrolateral periaqueductal gray; RPa; serotonin receptor, 2A subtype; raphe pallidus; sodium phosphate buffer; PB; brown adipose tissue; DRC; BAT; 5-HIAA; 8-hydroxy-N,N-dipropyl-2-aminotetralin; PBST; DRD; DRI; HC; lateral parabrachial nucleus, external lateral part; DA; 5-HT1A; 5-HT1B; 5-HT2A; Temperature; Rat; Serotonin; fos Gene; Lateral nucleus; Rodentia; Central nervous system; Stress; Encephalon; Serotoninergic neuron; Parabrachial nucleus; Vertebrata; Mammalia; Animal; Neurotransmitter; Raphe nucleus; Protooncogene; Immediate early gene
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2011.09.011

Abstract Physical (exteroceptive) stimuli and emotional (interoceptive) stimuli are thought to influence stress-related physiologic and behavioral responses through different neural mechanisms. Previous studies have demonstrated that stress-induced activation of brainstem serotonergic systems is influenced by environmental factors such as temperature. In order to further investigate the effects of environmental influences on stress-induced activation of serotonergic systems, we exposed adult male Wistar rats to either home cage control conditions or a 15-min swim in water maintained at 19 °C, 25 °C, or 35 °C and conducted dual immunohistochemical staining for c-Fos, a marker of immediate-early nuclear activation, and tryptophan hydroxylase (TPH), a marker of serotonergic neurons. Changes in core body temperature were documented using biotelemetry. As expected, exposure to cold (19 °C) swim, relative to warm (35 °C) swim, increased c-Fos expression in the external lateral part of the parabrachial nucleus (LPBel), an important part of the spinoparabrachial pathway involved in sensation of cold, cutaneous stimuli, and in serotonergic neurons in the raphe pallidus nucleus (RPa), an important part of the efferent mechanisms controlling thermoregulatory warming responses. In addition, exposure to cold (19 °C) swim, relative to 35 °C swim, increased c-Fos expression in the dorsal raphe nucleus, ventrolateral part/periaqueductal gray (DRVL/VLPAG) and dorsal raphe nucleus, interfascicular part (DRI). Both of these subregions of the dorsal raphe nucleus (DR) have previously been implicated in thermoregulatory responses. Altogether, the data are consistent with the hypothesis that midbrain serotonergic neurons, possibly via activation of afferents to the DR by thermosensitive spinoparabrachial pathways, play a role in integration of physiologic and behavioral responses to interoceptive stress-related cues involved in forced swimming and exteroceptive cues related to cold ambient temperature.