Effects of a selective 5‐HT<sub>2</sub> agonist, DOI, on 5‐HT neuronal firing in the dorsal raphe nucleus and 5‐HT release and metabolism in the frontal cortex

Wright, Ian K.; Garratt, Jeni C.; Marsden, C.A.

doi:10.1111/j.1476-5381.1990.tb14683.x

Cited by 79 publications

(23 citation statements)

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“…In addition, Carli and Samanin (1992) have found that 5-HT 2 receptor agonists (lysergic acid diethylamide and quipazine) cause a ritanserin-sensitive deterioration in choice accuracy and omission in the five-choice serial reaction time task, as seen here with the highest dose of DOI. In contrast, there is evidence suggesting presynaptic inhibition of serotonergic activity by DOI (Wright et al 1990). Altogether, DOI may not only activate 5-HT 2A receptors postsynaptically but also produce an indirect serotonergic inhibition (i.e.…”

Section: Discussionmentioning

confidence: 83%

“…If 8-OH-DPAT preferentially acts on the dorsal raphé, the stimulation of 5-HT 1A somatodendritic autoreceptors would reduce serotonergic neuronal firing and 5-HT release (Sprouse and Aghajanian 1988;Wright et al 1990). In contrast, the activation of postsynaptic 5-HT 1A receptors increases wakefulness and leads to its antidepressant-like activity (Leonard 1996;Bjorvatn and Ursin 1998).…”

Section: Discussionmentioning

confidence: 98%

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Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Nakamura¹,

Kurasawa²

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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Central serotonergic systems play an important role in regulating mood/emotion, cognition, sleep and wakefulness, appetite and locomotion and body temperature via multiple receptor subtypes. Among them, 5-HT1A and 5-HT2A/2C receptors have opposite effects with respect to certain functions. The aim of the present study was to compare the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT2A/2C receptor agonist, on the performance of middle-aged rats in a two-lever choice reaction task that assessed attention and vigilance functions. We also examined the effects of aniracetam, a cognition enhancer, and its major metabolites on the induced performance impairments. 8-OH-DPAT (0.3 mg/kg s.c.) reduced response speed and choice accuracy and increased response omission with a reduction of task-associated motor activity without inducing motor inability or motivational changes. These findings indicate a specific disturbance of attentional and vigilance processes. DOI caused similar impairments at the highest dose tested (3 mg/kg s.c.); at a lower dose (1 mg/kg s.c.), however, it selectively attenuated the response speed, suggesting a selective attention deficit. (-)-Alprenolol, a non-selective 5-HT1A receptor antagonist, and ritanserin, a preferential 5-HT2A receptor antagonist, blocked the 8-OH-DPAT- and DOI-induced performance impairments respectively. Aniracetam ameliorated all the performance deficits, and the metabolites N-anisoyl-GABA and 2-pyrrolidinone partially mimicked the aniracetam effect in the 8-OHDPAT-induced attentional and vigilance impairments. Nefiracetam, another cognition enhancer, improved only the 8-OH-DPAT-induced impairments. Each compound tested alone had no effect on task performance. These results indicate that both serotonergic regulations, possibly via presynaptic 5-HT1A receptors and more likely via postsynaptic 5-HT2A receptors, lead similarly to attention deficits.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 98%

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Nakamura¹,

Kurasawa²

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…Parallel effects on DRN discharge and 5-HT terminal release has also been shown for other compounds such as the 5-HT 1A agonist 8-OH-DPAT, which decreases both DRN discharge and terminal 5-HT release (Crespi et al 1990), 5-HT 2 agonists (Wright et al 1990), and serotonin-selective reuptake inhibitors (Romero et al 1996). Furthermore, parallel effects of CRF on LC discharge and terminal norepinephrine release have been demonstrated (Page and Abercrombie 1999;Curtis et al 1997;Smagin et al 1995).…”

Section: Discussionmentioning

confidence: 90%

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

Kirby

Rice

Valentino

2000

Neuropsychopharmacology

278

284

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The present study examined the regional localization of corticotropin-releasing factor (CRF)-and 5-hydroxytryptamine (5-HT)-immunoreactive (IR) fibers within the rat dorsal raphe nucleus (DRN) using immunohistochemistry. Additionally, the effects of CRF, administered intracerebroventricularly (0.1-3.0 g) or intraraphe (0.3-30 ng), on discharge rates of putative 5-HT DRN neurons Corticotropin-releasing factor (CRF) has a diverse range of physiological and behavioral effects, acting both as a neurohormone at the level of the anterior pituitary and as a neurotransmitter in brain. As a neurohormone, CRF initiates the release of adrenocorticotropic hormone which triggers the endocrine limb of the stress response . Anatomical evidence of a widespread distribution of CRF-immunoreactive (IR) terminals and receptors throughout the brain De Souza et al. 1985;Potter et al. 1994;Sakanaka et al. 1987;Swanson et al. 1983) provides support for the additional role of CRF as a brain neurotransmitter. An example of a potential neurotransmitter action of CRF is its action on the locus coeruleus (LC)-norepinephrine system. Intracerebroventricular (i.c.v.) or intracoerulear administration of CRF increases activity of LC neurons Page and Abercrombie 1999;Valentino et al. 1983) and stimulates NE release in terminal fields of the LC (Lavicky and Dunn 1993;Page and Abercrombie 1999;Smagin et al. 1995). Moreover, activation of LC neurons by certain physiological stimuli is attenuated by CRF antagonists administered into the LC (Curtis et al. 1994;Lechner et al. 1997).Anatomical evidence suggests that CRF is also positioned to affect activity of the dorsal raphe nucleus Philadelphia, PA 19102. Received May 17, 1999; revised July 28, 1999; accepted August 3, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 2 CRF Effects on 5-HT Neurons 149 (DRN)-5-hydroxytryptamine (5-HT) system. Thus, CRF receptor binding sites (De Souza et al. 1985) and mRNA Potter et al. 1994) as well as CRF-IR terminals (Sakanaka et al. 1987;Swanson et al. 1983) are localized in the DRN, a primary site of 5-HT cell bodies projecting to the forebrain. Recent studies demonstrated that relatively low doses of CRF (administered i.c.v.) inhibit 5-HT release in two different terminal regions of the DRN (i.e., striatum and lateral septum), suggesting that the site of action of CRF effects on 5-HT release is at the level of the cell bodies in the DRN . Consistent with this, electrophysiological recordings indicated that a low dose of CRF (administered i.c.v.) that decreased extracellular levels of 5-HT in striatum also decreased DRN discharge rate . In contrast to the effects of low doses of CRF, higher doses were found to not alter or to increase extracellular 5-HT levels in the lateral septum or striatum, respectively. The complex dose-related effects of CRF on 5-HT release could be a function of multiple CRF receptor subtypes within the DRN and/or different sites of action (cell bodies vs. terminals) of i.c.v. administered CRF.The present study was designed t...

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“…Either lateral attack, that would be part of an offensive strategy similar to the territorial behavior of a dominant male against an intruder, or frontal attack, that would be part of a defensive strategy similar to the reaction of a cornered animal to an inescapable threat (Lucion and De Almeida 1996), decreased after the administration of 8-OH-DPAT. Since 8-OH-DPAT decreases firing rate of raphe nuclei (Wright et al 1990;Jacobs and Fornal 1991), we may conclude that a reduction in the activity of the median raphe nucleus decreases maternal aggression.…”

Section: Discussionmentioning

confidence: 97%

8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats

Almeida

Lucion

1997

Psychopharmacology

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The purpose of the present study was to analyze the role of somatodendritic autoreceptors and postsynaptic 5-HT1A receptors in the modulation of maternal aggressive behavior. The 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) was microinjected (0.2, 0.5 and 2.0 microg/0.2 microl) in different brain areas of female Wistar rats: median raphe nucleus (MnR); medial septal area (MS); anterior corticomedial amygdaloid nucleus (ACoM); and dorsal periaqueductal gray (DPAG). The behaviors of lactating female rats with pups against a conspecific male intruder were recorded on day 7 post-partum. Results showed that in the median raphe nuclei, in the dorsal periaqueductal gray and in the corticomedial amygdaloid nucleus 8-OH-DPAT decreased maternal aggression; while in the medial septum, the intermediate dose (0.5 microg/0.2 microl) of the 5-HT1A receptor agonist increased the aggressive behavior of the lactating female rat. It is concluded that the main role of the 5-HT1A somatodendritic autoreceptors and the post-synaptic receptors of the brain areas studied is to decrease maternal aggression, however, at a specific dosage, 8-OH-DPAT acting on postsynaptic receptors of the medial septal area can increase aggressiveness.

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Effects of a selective 5‐HT₂ agonist, DOI, on 5‐HT neuronal firing in the dorsal raphe nucleus and 5‐HT release and metabolism in the frontal cortex

Cited by 79 publications

References 9 publications

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats

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Effects of a selective 5‐HT2 agonist, DOI, on 5‐HT neuronal firing in the dorsal raphe nucleus and 5‐HT release and metabolism in the frontal cortex

Cited by 79 publications

References 9 publications

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam

Effects of Corticotropin-Releasing Factor on Neuronal Activity in the Serotonergic Dorsal Raphe Nucleus

8-OH-DPAT in the median raphe, dorsal periaqueductal gray and corticomedial amygdala nucleus decreases, but in the medial septal area it can increase maternal aggressive behavior in rats

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Effects of a selective 5‐HT₂ agonist, DOI, on 5‐HT neuronal firing in the dorsal raphe nucleus and 5‐HT release and metabolism in the frontal cortex