Time-course of recovery of 5-HT1A receptors and changes in 5-HT1A receptor mRNA after irreversible inactivation with EEDQ

Raghupathi, Revathi K.; Brousseau, David A.; McGonigle, Paul

doi:10.1016/0169-328x(95)00311-f

Cited by 16 publications

(12 citation statements)

References 32 publications

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“…Recovery occurred at a slow rate with receptor density still 46% above control values on day 4 after cessation of MDL11,939 injections, and this was followed by a rapid and complete return to control receptor density between days 4 and 6. This time course of recovery is within the range of recoveries reported after down regulation of the D 1 receptor (5 days; Fuxe et al 1987), 5-HT 1A receptor (between 4 and 7 days; Raghupathi et al 1996), and 5-HT 2 receptor (6 days; Leysen and Pauwels 1990). The duration of the upregulation of the 5-HT 2A receptor in frontal cortex produced by MDL11,939 corresponded well with the accelerated rate of CR acquisition.…”

Section: Discussionsupporting

confidence: 62%

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

et al. 2004

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Section: Discussionsupporting

confidence: 62%

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

et al. 2004

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“…levels was within the same range for MDL11,939 (4 -8 days) and for BOL (5-8 days). These recovery times are within the range of recoveries reported after up-regulation of D 1 receptors (5 days; Fuxe et al, 1987), 5-HT 1A receptors (4 -7 days; Raghupati et al, 1996), and 5-HT 2A receptors (4 to 6 days; Harvey et al, 2004). These time courses are also in agreement with studies in which down-regulation of 5-HT 2 or 5-HT 2A receptor density returned to normal levels after 6 -10 days (Leysen and Pauwels, 1990;Kettle et al, 1999).…”

Section: Discussionsupporting

confidence: 80%

The Time-Course for Up- and Down-Regulation of the Cortical 5-Hydroxytryptamine (5-HT)_2A Receptor Density Predicts 5-HT_2A Receptor-Mediated Behavior in the Rabbit

Dave

Harvey²,

Aloyo³

2007

J Pharmacol Exp Ther

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5-Hydroxytryptamine (serotonin; 5-HT) 2 receptor agonists such as (Ϯ)-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) injected systemically or directly into frontal cortex, elicit stereotyped head movements that are mediated by 5-HT 2A receptors. Chronic administration of 5-HT 2A receptor antagonists can produce either a down-regulation, e.g., d-2-bromolysergic acid diethylamide (BOL) or an up-regulation, e.g., ␣-phenyl-10(2-phenylethyl)-4-piperidinemethanol (MDL11,939) of cortical 5-HT 2A receptors in the rabbit with no change in the density of the 5-HT 2C receptor. We examined the degree to which the time course for the onset and offset of changes in cortical 5-HT 2A receptor density was correlated with functional changes as measured by the magnitude of DOI elicited, 5-HT 2A receptor-mediated head movements (head bobs). First, the magnitude of DOI-elicited head bobs was measured over 1 to 8 days after chronic BOL (5.8 mol/kg), MDL11,939 (10 mol/ kg), or vehicle administration. Second, rabbits were injected with BOL, MDL11,939, or vehicle once daily for 8 days, and then, 1 to 8 days after the cessation of drug or vehicle, DOIelicited head bobs were determined. Samples of frontal cortex were obtained for each animal immediately following behavioral testing, and 5-HT 2A receptor density was measured using [ 3 H]ketanserin. Thus, each animal provided a value for receptor density and number of head bobs, and these two measures showed a high degree of correlation between 0.94 for BOL and 0.95 for MDL11,939. This study establishes that the density of 5-HT 2A receptors in cortex reflects their functional status.Perturbations in neurotransmission can lead to adaptations at the receptor level, resulting in a change in the functional status of an organism. These adaptations may include changes in receptor density and/or the receptor's interaction with its cognate second messenger system. For G proteincoupled receptors, chronic activation with agonists produces down-regulation of the receptor, whereas inactivation with antagonists results in up-regulation. Studies investigating the in vivo regulation of the 5-HT 2A receptor have shown that the adaptive changes are different from those in other receptor systems. The expected adaptive change after chronic administration of antagonists, i.e., an increase in the density of receptors (Creese and Sibley, 1981), was not observed. Unlike most G protein-coupled receptors (Tsao and von Zastrow, 2000), numerous studies demonstrated that chronic treatment with 5-HT 2A/2C antagonists down-regulated 5-HT 2A receptor density (for reviews see Roth et al., 1998;Gray and Roth, 2001). However, recently, up-regulation of cortical 5-HT 2A receptors has been reported for two 5-HT 2A antagonists, SR 46349B in the rodent (Rinaldi-Carmena et al., 1993a,b) and MDL11,939 in the rabbit (Aloyo et al., 2001). Although the mechanisms underlying 5-HT 2A receptor up-or down-regulation by antagonists are unknown, parallel changes in receptor-mediated behaviors have been demonstrated, suggesti...

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“…The inactivation of 5‐HT 1A receptors by the alkylating agent EEDQ (Meller et al , 1990; Cox et al , 1993) failed to affect basal dialysate 5‐HT, which would suggest that, under physiological conditions, the release of 5‐HT in this nucleus does not tonically activate such receptors. However, it should be taken into consideration that the systemic administration of EEDQ not only inactivates 5‐HT 1A and other 5‐HT receptor subtypes (Pinto & Battaglia, 1993; Gozlan et al , 1994; Raghupathi et al , 1996) but also other monoaminergic receptors (Norman & Creese, 1986; Nowak et al , 1988; Pilc & Vetulani, 1990). Therefore, the possibility that the lack of effect of systemic EEDQ on the basal release of 5‐HT in the MRN may be accounted for by a balance of opposing actions on different brain receptors cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

A microdialysis study of the in vivo release of 5‐HT in the median raphe nucleus of the rat

Adell

Artigas

1998

British J Pharmacology

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1 The present study has examined several characteristics of the release of 5-HT in the median raphe nucleus in terms of its dependence of nerve impulse, provenance of a vesicular storage fraction as well as the regulatory role played by 5-HT 1A receptors. 2 Tetrodotoxin (1 mM) and reserpine (5 mg kg 71 , i.p.) virtually suppressed the output of 5-HT. 3 The administration of EEDQ (10 mg kg 71 , i.p.) did not alter the basal release of 5-HT but abolished the reduction of 5-HT release induced by 8-OH-DPAT (0.1 mg kg 71 , s.c.). 4 The perfusion of 1 ± 100 mM of 8-OH-DPAT or the novel 5-HT 1A agonist BAY63702 decreased the eux of 5-HT, whereas the perfusion of the 5-HT 1A antagonist WAY-100635 failed to alter 5-HT release. 5 The decrease in dialysate 5-HT induced by 100 mM 8-OH-DPAT was reversed by the concurrent perfusion of 100 mM WAY-100635. Also, the perfusion of 100 mM WAY-100635 for 2 h inhibited partly the reduction of 5-HT release evoked by the systemic administration of 8-OH-DPAT (0.1 mg kg 71 ). 6 These results indicate that extracellular 5-HT in the median raphe nucleus is stored in vesicles and released in an impulse-dependent manner. Also, the basal release of 5-HT in the median raphe nucleus does not appear to be under the tonic control of somatodendritic 5-HT 1A receptors by endogenous 5-HT. Instead, this feedback mechanism seems to be triggered when an excess of the transmitter or a 5-HT 1A agonist is present in the extracellular space of the median raphe nucleus.

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Time-course of recovery of 5-HT1A receptors and changes in 5-HT1A receptor mRNA after irreversible inactivation with EEDQ

Cited by 16 publications

References 32 publications

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

The Time-Course for Up- and Down-Regulation of the Cortical 5-Hydroxytryptamine (5-HT)_2A Receptor Density Predicts 5-HT_2A Receptor-Mediated Behavior in the Rabbit

A microdialysis study of the in vivo release of 5‐HT in the median raphe nucleus of the rat

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Time-course of recovery of 5-HT1A receptors and changes in 5-HT1A receptor mRNA after irreversible inactivation with EEDQ

Cited by 16 publications

References 32 publications

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

Selective remodeling of rabbit frontal cortex: relationship between 5-HT 2A receptor density and associative learning

The Time-Course for Up- and Down-Regulation of the Cortical 5-Hydroxytryptamine (5-HT)2A Receptor Density Predicts 5-HT2A Receptor-Mediated Behavior in the Rabbit

A microdialysis study of the in vivo release of 5‐HT in the median raphe nucleus of the rat

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The Time-Course for Up- and Down-Regulation of the Cortical 5-Hydroxytryptamine (5-HT)_2A Receptor Density Predicts 5-HT_2A Receptor-Mediated Behavior in the Rabbit