A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze

Woolley, Marie L.; Bentley, Jane; Sleight, Andrew J.; Marsden, C.A.; Fone, Kevin C. F.

doi:10.1016/s0028-3908(01)00056-9

Cited by 193 publications

(126 citation statements)

References 25 publications

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“…These data further support the notion that 5-HT 6 receptor antagonists have cognitionenhancing properties (Rogers and Hagan, 2001;Woolley et al, 2001Woolley et al, , 2004. Comparing the dose-related effects of Ro4368554 across both drug-induced deficit models revealed a similar pattern.…”

Section: Effects Of Ro4368554supporting

confidence: 82%

“…SB271046 (Bromidge et al, 1999) and Ro046790 were the first 5-HT 6 antagonists to be evaluated for their behavioral effects, and both compounds improved retention in a Morris water maze task in rats, suggesting an improvement of spatial memory (Rogers and Hagan, 2001;Woolley et al, 2001). Ro046790 enhanced nonspatial working memory in an object recognition task (ORT) (Woolley et al, 2003), increased consolidation in an autoshaping task, and reversed scopolamine-induced deficits in both an autoshaping and a passive avoidance task (Bos et al, 2001;Meneses, 2001).…”

Section: Introductionmentioning

confidence: 99%

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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

136

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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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Section: Effects Of Ro4368554supporting

confidence: 82%

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

136

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“…However, studies of the roles of 5-HT 6 Rs in these and other behavioral processes have produced conflicting results. With regard to cognition, rats acutely treated with 5-HT 6 R antagonists demonstrated improved spatial memory retention 1 week after Morris maze training (Woolley et al, 2001;Stean et al, 2002). 5-HT 6 R antagonists also enhanced acquisition and reversed a scopolamine-evoked deficit in rat operant autoshaping and passive avoidance tasks (Bos et al, 2001;Meneses, 2001;Riemer et al, 2003).…”

Section: -Ht 6 R-influenced Behaviorsmentioning

confidence: 99%

“…Thus, the expression pattern and pharmacological properties of Rs indicate that they may contribute to serotonergic modulation of clinically relevant neuropsychological processes and psychopharmacological responses. Administration of 5-HT 6 R antagonists and antisense oligonucleotides have been reported to produce several behavioral effects in rodents, including feeding suppression (Svartengren et al, 2004), yawning and stretching (Bourson et al, 1995;Sleight et al, 1996;Sleight et al, 1998;Bentley et al, 1999), decreased anxiety-related behaviors (Hamon et al, 1999), and improved performance in learning and memory tasks (Meneses, 2001;Rogers and Hagan, 2001;Woolley et al, 2001;Russell and Dias, 2002;Lindner et al, 2003;Riemer et al, 2003).…”

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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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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“…Initial experiments did not provide any evidence for the involvement of the 5-HT6 receptor in satiety [110]. Studies using either intracerebroventricular injections of 5-HT6 antisense oligonucleotides or intraperitoneal administration of the 5-HT6 receptor antagonist Ro 04-6790 found decreased feeding behaviour and body weight gain [111], [112]. The 5-HT6 partial agonist E-6837 induced hypophagia in a rat model of dietinduced-obesity (DIO) [113], and mice carrying a non-functional 5-HT6 receptor do not become obese when exposed to a high fat diet [114].…”

mentioning

confidence: 99%

Serotonin controlling feeding and satiety

Voigt

Fink

2015

Behavioural Brain Research

266

167

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Serotonin has been implicated in the control of satiety for almost four decades. Historically, the insight that the appetite suppressant effect of fenfluramine is linked to serotonin has stimulated interest in and research into the role of this neurotransmitter in satiety. Various rodent models, including transgenic models, have been developed to identify the involved 5-HT receptor subtypes. This approach also required the availability of receptor ligands of different selectivity, and behavioural techniques had to be developed simultaneously which allow differentiating between unspecific pharmacological effects of these ligands and 'true' 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 IntroductionWhat are the behavioural and physiological mechanisms that promote satiety? How is satiety defined? Satiety can be seen as a behavioural state which arises from food consumption and suppresses the initiation of eating for a particular period of time [1]. This description alone suggests a high degree of complexity as peripheral post-ingestive and post-absorptive signals need to be relayed to the brain where they are integrated with other signals to produce (or not) the behavioural state called satiety. The state of satiety is brought about a process called satiation, where sensory, cognitive and early post-ingestive mechanisms bring feeding to a halt and thus stopping a meal. Promoting satiation alone must not necessarily lead to reduced total food intake as the frequency of meals could be increased subsequently. Many peripheral and brain mechanisms have been identified that are involved in the expression satiety and it has been suggested that serotonin accelerates satiation and prolongs satiety [2]. In the following, we will review the role of serotonin in satiety in more detail 1 . The reader will see that, despite immense progress made during the last years, the field is still far from being resolved.As serotonin (5-Hydroxytryptamine; 5-HT) is a phylogenetically old neurotransmitter, various functions had time to evolve in different phyla, but maybe also in different species. 5-HT receptors exist in animal cells for millions of years and they are as old as adrenoreceptors ore some peptide receptors, possibly even older [5,6]. Even in invertebrates such as molluscs (Aplysia californica) and annelids (Hirudo medicinalis), 5-HT might functionally be related to food intake [7]. 5-HT is involved in feeding even in the honeybee where it has separate effects in the gut and in the insect brain [8]. In general, however, 5-HT seems rather to be involved in appetitive behaviours in invertebrates whereas it has more of a satiating effect in vertebrates [9]. In general, 5-HT neurons seem to be more extensively distributed throughout the body in lower animals than in higher animals including mammals where 5-HT neurones...

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A role for 5-ht6 receptors in retention of spatial learning in the Morris water maze

Cited by 193 publications

References 25 publications

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

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

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

Serotonin controlling feeding and satiety

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