Abstract
Serotonergic systems arising from the mid-rostrocaudal and caudal dorsal raphe nucleus (DR) have been implicated in the facilitation of anxiety-related behavioral responses to anxiogenic drugs or aversive stimuli. In this study we attempted to determine a threshold to engage serotonergic neurons in the DR following exposure to aversive conditions in an anxiety-related behavioral test. We manipulated the intensity of anxiogenic stimuli in studies of male Wistar rats by leaving them undisturbed (CO), briefly handling them (HA), or exposing them to an open-field arena for 15-min under low-light (LL: 8–13lx) or high-light (HL: 400–500lx) conditions. Rats exposed to HL conditions responded with reduced locomotor activity, reduced time spent exploring the center of the arena, a lower frequency of rearing and grooming, and an increased frequency of facing the corner of the arena compared to LL rats. Rats exposed to HL conditions had small but significant increases in c-Fos expression within serotonergic neurons in subdivisions of the rostral DR. Exposure to HL conditions did not alter c-Fos responses in serotonergic neurons in any other DR subdivision. In contrast, rats exposed to the open-field arena had increased c-Fos expression in non-serotonergic cells throughout the DR compared to CO rats, and this effect was particularly apparent in the dorsolateral part of the DR. We conclude that exposure to HL conditions, compared to LL conditions, increased anxiety-related behavioral responses in an open-field arena but this stimulus was at or below the threshold required to increase c-Fos expression in serotonergic neurons.
Highlights
Serotonin (5-hydroxytryptamine; 5-HT) influences a variety of behavioral and physiological processes including arousal, sleep-wake cycles, food intake, and anxiety-related behavior [15;21;31;36]
Rats exposed to the HL condition never visited the small center while 5 of 8 rats exposed to the LL condition visited the small center; there was no statistical difference between the LL and HL rats in the percentage of time spent in the small center
We found no evidence for greater c-Fos expression in serotonergic or nonserotonergic neurons in rats exposed to the HL condition, compared to rats exposed to the LL condition, within any subdivision of the dorsal raphe nucleus (DR) studied
Summary
Serotonin (5-hydroxytryptamine; 5-HT) influences a variety of behavioral and physiological processes including arousal, sleep-wake cycles, food intake, and anxiety-related behavior [15;21;31;36]. The central 5-HT network includes various nuclei in the brainstem of which the dorsal raphe nucleus (DR) is an important structure containing over 50% of all 5-HT neurons projecting to the forebrain [65]. It has become evident that the DR is a heterogeneous nucleus containing various anatomically, neurochemically, and functionally distinct subdivisions that have their own afferents and efferents and are responsive to different types of stimuli [16;30;31;37;43]. The immediate-early gene product c-Fos is broadly expressed throughout the brain in response to a variety of challenges, which makes it a powerful tool to study intracellular responses of specific neurons in the brain under various conditions [10], as it can be combined with characterization of the neurochemical properties of the responsive neurons
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