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

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.