Effects of Microinjections of 5,7-Dihydroxytryptamine in the Suprachiasmatic Nuclei of the Rat on Serotonin Reuptake and the Circadian Variation of Corticosterone Levels

Williams, Jonathan; Miall‐Allen, V M; Klinowski, Margaret; Azmitia, Efrain C.

doi:10.1159/000123494

Cited by 30 publications

(4 citation statements)

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“…This is in agreement with previous work showing that treatments that increase or decrease 5-HT activity can induce phase shifts (Honma et al, 1979;Witz-Justice and Campbell, 1982;Williams et al, 1983;Smale et al, 1990). In addition, previous studies have demonstrated increased 5-HT activity in the SCN at night (Hery et al, 1982;Faradji et al, 1983;Ramirez et al, 1987).…”

Section: Discussionsupporting

confidence: 93%

“…Earlier studies have suggested that this projection can modulate SCN clock functioning, although it is not essential for the clock to operate. Some studies found that raphe lesions or chemical treatments that deplete brain 5-HT levels decrease the amplitude (Block and Zucker, 1976; Kam and Moberg, 1977;Szafarczyk et al, 1979) or change the phase (Honma et al, 1979;Williams et al, 1983;Smale et al, 1990) of circadian rhythms, although other studies found these treatments to have no effect on circadian rhythms (Moore and Klein, 1974;Balestrery and Moberg, 1976). In addition, injections of a monoamine oxidase inhibitor or 5-HT uptake blocker, both of which increase 5-HT levels, can phase-shift circadian rhythms in vivo (Wirz-Justice and Campbell, 1982).…”

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confidence: 99%

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Serotonin and the Mammalian Circadian System: I. In Vitro Phase Shifts by Serotonergic Agonists and Antagonists

et al. 1993

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The primary mammalian circadian clock, located in the suprachiasmatic nuclei (SCN), receives a major input from the raphe nuclei. The role of this input is largely unknown, and is the focus of this research. The SCN clock survives in vitro, where it produces a 24-hr rhythm in spontaneous neuronal activity that is sustained for at least three cycles. The sensitivity of the SCN clock to drugs can therefore be tested in vitro by determining whether various compounds alter the phase of this rhythm. We have previously shown that the nonspecific serotonin (5-HT) agonist quipazine resets the SCN clock in vitro, inducing phase advances in the daytime and phase delays at night. These results suggest that the 5-HT-ergic input from the raphe nuclei can modulate the phase of the SCN circadian clock. In this study we began by using autoradiography to determine that the SCN contain abundant 5-HT1A and 5-HT1B receptors, very few 5-HT1C and 5-HT2 receptors, and no 5-HT3 receptors. Next we investigated the ability of 5-HT-ergic agonists and antagonists to reset the clock in vitro, in order to determine what type or types of 5-HT receptor(s) are functionally linked to the SCN clock. We began by providing further evidence of 5-HT-ergic effects in the SCN. We found that 5-HT mimicked the effects of quipazine, whereas the nonspecific 5-HT antagonist metergoline blocked these effects, in both the day and night. Next we found that the 5-HT1A agonist 8-OH-DPAT, and to a lesser extent the 5-HT1A-1B agonist RU 24969, mimicked the effects of quipazine during the subjective daytime, whereas the 5-HT1A antagonist NAN-190 blocked quipazine's effects. None of the other specific agonists or antagonists we tried induced similar effects. This suggests that quipazine acts on 5-HT1A receptors in the daytime to advance the SCN clock. None of the specific agents we tried were able either to mimic or to block the actions of 5-HT or quipazine at circadian time 15. Thus, we were unable to determine the type of 5-HT receptor involved in nighttime phase delays by quipazine or 5-HT. However, since the dose-response curves for quipazine during the day and night are virtually identical, we hypothesize that the nighttime 5-HT receptor is a 5-HT1-like receptor.

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Section: Discussionsupporting

confidence: 93%

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confidence: 99%

Serotonin and the Mammalian Circadian System: I. In Vitro Phase Shifts by Serotonergic Agonists and Antagonists

et al. 1993

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“…The involvement of 5-HT fibres in the regulation of CRF neurons is further supported by the findings that restraint stress increases both binding at 5-HT 1A receptors in hippocampus (Mendelson & McEwen, 1991) and 5-HT turnover in the anterior hypothalamus (De Souza & Van Loon, 1986), that fenfluramine (McElroy et ai, 1984;Van de Kar et al, 1985), 5-HT (Leibowitz et al, 1989) and 5-HT agonists (Calogero et ai, 1990; Owens et al, 1990Owens et al, , 1991 stimulate corticosteroid secretion, and that injection of the selective neurotoxin 5,7-DHT into the raphe nuclei reduces the adrenocortical response to neurogenic stress (Feldman et al, 1984). More selectivelesions of 5-HT terminals, through injection of 5,7-DHT into the PVN, completely block the rise in plasma corticosterone on photic or electrical stimulation of the dorsal hippocampus (Feldman et al, 1987), while injection of 5,7-DHT in the suprachiasmatic nucleus alters the circadian variations of the HPA axis (Williams et al, 1983). Furthermore, fluoxetine, which inhibits 5-HT reuptake (Gibbs& , and dextrofenfluramine, which also stimulates 5-HT release from terminals (Guillaume, 1989), both increase CRF concentration in hypophyseal portal blood.…”

Section: Control Of the Activity Of Crf Neuronsmentioning

confidence: 99%

Glucocorticoids, Transmitters and Stress

et al. 1992

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Many kinds of stress stimulate the neuroendocrine systems controlling catecholamine and glucocorticoid secretion. Stress-induced stimulation of CRF-containing neurons appears to be mediated by serotonergic, noradrenergic, and possibly other neuronal pathways. Stress can alter various neurobiological and endocrine functions, two essential components of the neuroendocrine responses being release of adrenalin from chromaffin cells of the adrenal medulla and secretion of glucocorticoids from adrenocortical cells. Activation of adrenal steroid secretion is mainly by a reflex activation of hypothalamic neurons, which stimulate ACTH secretion from the anterior pituitary. While the neuropeptide CRF plays a major role in the neuroendocrine response to stress, the neuronal signals which are responsible for the regulation of CRF neurons have not been completely elucidated. A number of other regulatory substances may also participate, alone or with CRF, in the control of ACTH secretion by pituitary corticotrophs, and there is increasing evidence that classical neurotransmitters or neuropeptides may act directly on adrenocortical cells to modulate corticosteroid secretion. We review the neuronal, neuroendocrine, and humoral pathways which participate in the regulation of stress-induced corticosteroid secretion, and present preliminary data on the effect of the tricyclic antidepressant, tianeptine in the response of the HPA axis to stress.

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“…Circadian rhythms can be disrupted to varying degrees by 5-HT depletion via PCPA (Szafarczyk et al, 1979), by lesions of the midbrain raphe nuclei (Levine et al, 1986), or by localized chemical lesions of 5-HT-ergic terminals in the SCN (Williams et al, 1983). Circadian rhythms can be disrupted to varying degrees by 5-HT depletion via PCPA (Szafarczyk et al, 1979), by lesions of the midbrain raphe nuclei (Levine et al, 1986), or by localized chemical lesions of 5-HT-ergic terminals in the SCN (Williams et al, 1983).…”

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confidence: 99%

Serotonin and the Mammalian Circadian System: II. Phase-Shifting Rat Behavioral Rhythms with Serotonergic Agonists

et al. 1993

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The suprachiasmatic nuclei (SCN) receive primary afferents from the median and dorsal raphe, but the role of these projections in circadian timekeeping is poorly understood. Studies of the SCN in vitro suggest that quipazine, a general serotonin (5-HT) receptor agonist, can produce circadian time-dependent phase advances and phase delays in circadian rhythms of neuronal activity. The present study addresses whether quipazine and the selective 5-HT1A receptor agonist 8-OH-DPAT are similarly effective in vivo. Drinking and wheel-running patterns of male Wistar rats individually housed in constant darkness were monitored before and after subcutaneous administration of quipazine (5-10 mg/kg) at either circadian time (CT) 6 or CT 18, with and without running wheels available. Dose-dependent phase advances (20-180 min) were produced at CT 6. Significant phase shifts were not observed at CT 18. CT 6 quipazine-treated animals also showed a sustained and significant shortening of rhythm period (tau) following treatment (-0.28 hr; p < 0.002). tau shortening was inconsistently observed in CT 18 quipazine-treated rats. Neither quipazine-induced phase shifts nor tau effects were dependent on wheel-running activity per se. 8-OH-DPAT delivered via intracerebral ventricular treatment into the third ventricle (5 microliters at 100 microM in saline) produced slightly smaller phase advances (20-90 min) at CT 6, but did not produce phase delays at CT 18 or changes in tau. These findings support in vitro evidence that 5-HT-ergic agonists can phase-shift the circadian pacemaker.

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Effects of Microinjections of 5,7-Dihydroxytryptamine in the Suprachiasmatic Nuclei of the Rat on Serotonin Reuptake and the Circadian Variation of Corticosterone Levels

Cited by 30 publications

References 31 publications

Serotonin and the Mammalian Circadian System: I. In Vitro Phase Shifts by Serotonergic Agonists and Antagonists

Serotonin and the Mammalian Circadian System: I. In Vitro Phase Shifts by Serotonergic Agonists and Antagonists

Glucocorticoids, Transmitters and Stress

Serotonin and the Mammalian Circadian System: II. Phase-Shifting Rat Behavioral Rhythms with Serotonergic Agonists

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