The distribution of 5-HT6 receptors in rat brain: an autoradiographic binding study using the radiolabelled 5-HT6 receptor antagonist [125I]SB-258585

Roberts, Jennifer; Reavill, Charlie; East, S Z; Harrison, Paul J.; Patel, Sara; Routledge, Carol; Leslie, R.A.

doi:10.1016/s0006-8993(02)02360-0

Cited by 135 publications

(86 citation statements)

References 11 publications

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“…A 4.2 kb band was apparent for wild-type, but not mutant samples; an approximate 50% reduction in the abundance of intact transcript was observed for heterozygotes ( Figure 1d). We attempted to confirm loss of protein product via autoradiography using the ligand 125 I-SB258585 (Roberts et al, 2002); however, we were unable to detect specific binding in wild-type brains. This finding is consistent with recent observations indicating that the affinities of ligands used to characterize 5-HT 6 Rs in the rat (such as 125 I-SB258585) demonstrate reduced affinity for the mouse homolog, and that 5-HT 6 R expression levels in the mouse are reduced relative to those in the rat (Hirst et al, 2003).…”

Section: Generation Of 5-ht 6 R Null Mutant Micementioning

confidence: 99%

“…This is the case for the 5-HT 6 R, a G-protein-coupled receptor that is positively linked to the adenylate cyclase second messenger system (Monsma et al, 1993;Ruat et al, 1993;Kohen et al, 1996;Branchek and Blackburn, 2000). Receptor expression in rats, guinea pigs, and humans appears CNS-limited and most prominent in the caudate-putamen, nucleus accumbens, and olfactory tubercle, with lesser expression in the hippocampus, cortex, and amygdala (Monsma et al, 1993;Ruat et al, 1993;Ward et al, 1995;Kohen et al, 1996;Roberts et al, 2002). Several classes of psychotropic drugs such as atypical antipsychotics, tricyclic antidepressants, and hallucinogens bind with high affinity to 5-HT 6 Rs (Monsma et al, 1993;Roth et al, 1994;Glatt et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

Bonasera

Chu

Brennan

et al. 2006

Neuropsychopharmacol

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The anatomical distribution and pharmacology of serotonin 6 receptors (5-HT 6 Rs) implicate them as contributors to the serotonergic regulation of complex behavior. To complement the limited range of pharmacological tools available to examine 5-HT 6 R function, we have generated a mouse line bearing a constitutive null mutation of the 5-HT 6 R gene. No perturbations of baseline behavior were noted in a wide array of assays pertinent to multiple neurobehavioral processes. However, 5-HT 6 R mutant mice demonstrated reduced responses to the ataxic and sedative effects of ethanol. No differences in ethanol metabolism were evident between wild-type and 5-HT 6 R mutant mice. These findings implicate 5-HT 6 Rs in the serotonergic modulation of responses to ethanol.

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Section: Generation Of 5-ht 6 R Null Mutant Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

Bonasera

Chu

Brennan

et al. 2006

Neuropsychopharmacol

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“…These include brain structures associated with learning and memory processes such as the hippocampus and the cerebral cortex (Gerard et al, 1997;Roberts et al, 2002;Ruat et al, 1993). Antagonism of 5-HT 6 receptors leads to an increase in the release of acetylcholine (Ach) (Riemer et al, 2003;ShiraziSouthall et al, 2002), but whether this is directly caused by antagonism at these receptors is still under debate.…”

Section: Introductionmentioning

confidence: 99%

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

Lieben

Blokland

Şık

et al. 2005

Neuropsychopharmacol

135

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Antagonists at serotonin type 6 (5-HT 6 ) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT 6 antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic-(tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT 6 receptor antagonists.

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“…Finally, selective lesion of 5-HT neurons by injection of 5,7-dihydroxytryptamine (5,7-DHT) in the DRN has been shown to not affect the levels of 5-HT 6 mRNA in the striatum of rat brain, thus confirming the postsynaptic localization of this receptor with respect to 5-HT neurons innervating this area (Gerard et al, 1996). Similarly, the lack of any difference in the levels of protein binding, following 6-OHDA selective lesion of the nigrostriatal pathway, demonstrates that the 5-HT 6 is also not located on membranes of DA neurons (Roberts et al, 2002).…”

Section: Striatummentioning

confidence: 66%

“…Finally, with regards to the last three 5-HT receptor families, only moderate-to-low concentrations of both receptor proteins and mRNA have been found in the SN and the GP of rat and human brain for the 5-HT 5A (Rees et al, 1994;Oliver et al, 2000), 5-HT 6 (Kohen et al, 1996;430 Gerard et al, 1997;Hamon et al, 1999;Roberts et al, 2002;Hirst et al, 2003) and 5-HT 7 (Ruat et al, 1993b;Martin-Cora and Pazos, 2004;Varnas et al, 2004) receptor subtypes.…”

Section: Substantia Nigra and Globus Pallidusmentioning

confidence: 99%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

133

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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The distribution of 5-HT6 receptors in rat brain: an autoradiographic binding study using the radiolabelled 5-HT6 receptor antagonist [125I]SB-258585

Cited by 135 publications

References 11 publications

A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

A Null Mutation of the Serotonin 6 Receptor Alters Acute Responses to Ethanol

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

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