Serotonin1A receptor agonists induce Fos protein expression in the locus coeruleus of the conscious rat

Hamamura, Takashi; Lee, Youmei; Fujiwara, Yutaka; Kuroda, Shigetoshi

doi:10.1016/s0006-8993(97)00332-6

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…We also found that, like 8-OH-DPAT, the active S(-)-enantiomer of the partial 5-HT 1A receptor agonist (Ϯ)-MDL 73005EF markedly increased the number of Fos positive cells in the LC, while the inactive, R(ϩ)-enantiomer did not. Consistent with the above findings, it was recently reported by Hamamura et al (1997) that the buspironerelated, 5-HT 1A receptor ligands tandospirone and ipsapirone increase Fos-LI in the LC, an effect blocked by the 5-HT 1A receptor antagonist, WAY 100135.…”

Section: Discussionsupporting

confidence: 88%

Effect of 5-HT1A receptor ligands on Fos-like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission

Hajós‐Korcsok

Sharp

1999

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This study investigated the effects of 8-OH-DPAT and various other 5-HT(1A) receptor agonists on brain noradrenergic transmission using Fos-like immunoreactivity (Fos-LI) as a marker of neural activation. Administration of 8-OH-DPAT (0.1 and 1 mg/kg) induced a marked and dose-related increase in the number of cells positive for Fos-LI in the locus coeruleus (LC), the main source of noradrenergic projections to the forebrain. This effect was also induced by the non-selective, partial 5-HT(1A) receptor agonist buspirone (10 mg/kg). The effect of both 8-OH-DPAT (0.1 mg/kg) and buspirone (10 mg/kg) on Fos-LI in the LC was blocked by pretreatment with the selective 5-HT(1A) receptor antagonist WAY 100635 (1 mg/kg). The active S(-)-enantiomer of the partial 5-HT(1A) receptor agonist (+/-)-MDL 75005EF (1 mg/kg) also induced the expression of Fos-LI in the LC, whereas the inactive R(+)-enantiomer of (+/-)-MDL 73005EF at the same dose did not. In addition to the LC, 8-OH-DPAT (0.1 mg/kg) also induced a marked increase in Fos-LI in various forebrain areas including the medial prefrontal cortex (infralimbic and cingulate cortical areas). More detailed analysis of the Fos response to 8-OH-DPAT in the medial prefrontal cortex revealed that the effect was attenuated by pretreatment with a combination of the beta(1)- and beta(2)-adrenoceptor antagonists ICI 118551 (4 mg/kg) and metoprolol (4 mg/kg), but not the alpha(1)-adrenoceptor antagonist prazosin (5 mg/kg). Taken together, the present findings provide immunocytochemical evidence that 5-HT(1A) receptor agonists activate noradrenergic neurones in the LC and that this leads to increased noradrenergic transmission at postsynaptic sites in the forebrain (specifically medial prefrontal cortex).

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Section: Discussionsupporting

confidence: 88%

Effect of 5-HT1A receptor ligands on Fos-like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission

Hajós‐Korcsok

Sharp

1999

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“…The 5-HT 1A receptors are not stimulated tonically because WAY 100635 given alone did not modify NA release (Hajós-Korcsok and Sharp, 1996). As an immunocytochemical marker of noradrenergic neuronal activation, the 5-HT 1A receptor agonists ipsapirone and tandospirone (Hamamura et al, 1997) as well as 8-OH-DPAT and MDL 73005EF were shown to increase the expression of the immediate early gene c-fos in the locus coeruleus, an effect sensitive to antagonism by WAY 100135 (Hamamura et al, 1997) or WAY 100635 (Hajós-Korcsok and.…”

Section: A General Aspectsmentioning

confidence: 99%

5-HT Receptor Regulation of Neurotransmitter Release

Fink¹,

Göthert²

2007

Pharmacol Rev

325

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“…Although all these effects suggest the neuronal circuit that is probably engaged in propagation of the effects initiated by blockade of NMDA receptors, and brain structures involved in the beneficial action of WAY 100135 on the disruptive effects evoked by MK-801, they do not allow for simple association of the above psychotomimetic effects of MK-801 with the enhancement of serotonin release and turnover (Whitton et al 1992) after similar doses of MK-801 (Loscher et al 1991;W dzony et al 1997) since, activation of somatodendritic 5-HT1A receptors decreases the release of serotonin from terminals (Sharp et al 1989). One possible explanation of this discrepancy is that the activation of 5-HT1A receptors due to an excessive release of serotonin after administration of MK-801 may activate neurons of the locus coeruleus (Hajos-Korcsok and Sharp 1999; Hamamura et al 1997;Piercey et al 1994), and subsequently enhance noradrenaline release (Hajos-Korcsok and Sharp 1996). Although it would be worthwhile to verify this neuronal circuit, it seems of interest that the detrimental effect of MK-801, injected to the ȩ ȩ ȩ ȩ Figure 5.…”

Section: Prepulse-induced Inhibition Of Acoustic Startle Responsementioning

confidence: 99%

WAY 100135, an Antagonist of 5-HT1A Serotonin Receptors, Attenuates Psychotomimetic Effects of MK-801

Wędzony

Maćkowiak

Zaja̧czkowski

et al. 2000

Neuropsychopharmacology

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Non-competitive antagonists of NMDA receptors such as phencyclidine (PCP) or ketamine are known for their strong, frequently neuroleptic-resistant psychotomimetic effects in humans (Javitt and Zukin 1991). These clinical effects, as well as evidence suggesting the involvement of NMDA receptors in the pathophysiology of schizophrenia (Carlsson et al. 1999;Harrison 1999;Wachtel and Turski 1990), support the experimental modeling of psychoses by administration of non-competitive NMDA receptor antagonists (Jentsch and Roth 1999). In this respect, MK-801 seems to be of special interest in experimental pharmacology. It belongs to a class of non-competitive NMDA receptor antagonists (Seeburg 1993;Lodge and Johnson 1990; Willetts et al. 1990) and MK-801 seems to be highly specific to the PCP binding site located in the ion channel of the NMDA receptor complex (Lodge and Johnson 1990;Seeburg 1993 (Carlsson 1993;Maj et al. 1991), impairment of sensorimotor gating (Mansbach and Geyer 1989; W dzony et al. 1994), and detrimental effects on spatial working memory (Verma and Moghaddam 1996). Although it is generally agreed that the psychostimulant and psychotomimetic effects of PCP, ketamine, and MK-801 are initiated by blockade of the NMDA receptor ion channel complex, the neuronal pathways or neurotransmitter systems involved in the propagation of the psychotomimetic effects are not precisely known (Bakshi and Geyer 1998). Moreover, the apparent lack of chemical compounds which might directly abolish the pharmacological blockade of these NMDA receptors (Lodge and Johnson 1990; Willetts et al. 1990), and prevent impairments of their function during the course of schizophrenia (Harrison 1999) justifies attempts to define neuroanatomical/neurochemical systems responsible for the propagation of the effects of non-competitive NMDA receptors.Apart from the dopaminergic system (Jentsch and Roth 1999), traditionally linked with psychotomimetic effects of non-competitive antagonists of NMDA receptors, and the noradrenergic system [currently under investigation (Bakshi and Geyer 1998, 1999;Jentsch et al. 1998)], considerable interest has been focused on serotonin and its receptors (Geyer 1998). It has been shown, for example, that MK-801 increases serotonin release (Whitton et al. 1992) and influences serotonin turnover (Loscher et al. 1991;W dzony et al. 1997). Moreover, the psychostimulant and psychotomimetic effects of MK-801 and PCP are attenuated by specific antagonists of 5-HT2A receptors (Schmidt and Fadayel 1996;Varty et al. 1999;Varty and Higgins 1995).Apart from 5-HT2A receptors, a growing number of studies indicate that MK-801 may also influence other serotonin receptors; for example, it increases mRNA of 5-HT6 and 5-HT7 receptors (Healy and Meador-Woodruff 1999). Moreover, the increased density of 5-HT1A receptors after a single administration of MK-801 has been reported in one of our recent studies (W dzony et al. 1997). The possible involvement of 5-HT1A receptors in the psychotomimetic effects of NMDA receptor antagon...

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Serotonin1A receptor agonists induce Fos protein expression in the locus coeruleus of the conscious rat

Cited by 15 publications

References 15 publications

Effect of 5-HT1A receptor ligands on Fos-like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission

Effect of 5-HT1A receptor ligands on Fos-like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission

5-HT Receptor Regulation of Neurotransmitter Release

WAY 100135, an Antagonist of 5-HT1A Serotonin Receptors, Attenuates Psychotomimetic Effects of MK-801

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