Mice overexpressing the 5-hydroxytryptamine transporter show no alterations in feeding behaviour and increased non-feeding responses to fenfluramine

Pringle, A.; Jennings, Katie A.; Line, Samantha J.; Bannerman, David M.; Higgs, Suzanne; Sharp, Trevor

doi:10.1007/s00213-008-1206-8

Cited by 23 publications

(13 citation statements)

References 44 publications

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“…These results also concord with studies associating the s allele of the 5-HTTLPR with obesity (Sookoian et al, 2007; Sookoian et al, 2008; Lan et al, 2009). As these animals have previously been found to display normal feeding behaviour (Pringle et al, 2008), 5-HTT overexpression may result in peripheral metabolic or developmental changes. It is also interesting to note that there are indications that the genetic manipulation had a larger effect on the body weight of males than females.…”

Section: Discussionmentioning

confidence: 96%

Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice

Line

Barkus

Coyle

et al. 2011

European Neuropsychopharmacology

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Human gene association studies have produced conflicting findings regarding the relationship between the 5-HT transporter (5-HTT) and anxiety. In the present study genetically modified mice were utilised to examine the effects of changes in 5-HTT expression on anxiety. In addition, the influence of 5-HTT expression on two innate “species-typical” behaviours (burrowing and marble burying) and body weight was explored. Across a range of models, 5-HTT overexpressing mice displayed reduced anxiety-like behaviour whilst 5-HTT knockout mice showed increased anxiety-like behaviour, compared to wildtype controls. In tests of species-typical behaviour 5-HTT overexpressing mice showed some facilitation whilst 5-HTT knockout mice were impaired. Reciprocal effects were also seen on body weight, as 5-HTT overexpressors were lighter and 5-HTT knockouts were heavier than wildtype controls. These findings show that variation in 5-HTT gene expression produces robust changes in anxiety and species-typical behaviour. Furthermore, the data add further support to findings that variation of 5-HTT expression in the human population is linked to changes in anxiety-related personality traits.

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Section: Discussionmentioning

confidence: 96%

Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice

Line

Barkus

Coyle

et al. 2011

European Neuropsychopharmacology

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“…The high variability between studies contrasts with relatively good convergence among studies measuring meal numbers in rats [6,23–25]. Closer analysis of feeding, as well as the relationship of activity or rest periods to eating in mice [26] will be needed to better understand these discrepancies. The absolute meaning of a particular meal pattern in mice may be unclear at the present time, but differences in patterns across conditions using a uniform criterion should be meaningful.…”

Section: Discussionmentioning

confidence: 99%

Meal patterns of mice under systematically varying approach and unit costs for food in a closed economy

Atalayer

Rowland

2009

Physiology & Behavior

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Several field and experimental studies have investigated the behavioral economics of food intake. In the laboratory, operant behavior has been used to emulate cost and to generate demand functions that express the relationship between the price of food and amount consumed. There have been few such studies of motivated food seeking and intake in mice, and none has reported demand functions. Using albino (CD1) male mice, the present study compares food intake and meal patterns across a series of ratio cost schedules. The first experiment examined unit price. A closed economy was used in which the mice were in the test chambers for 23 h/day and earned all of their food via either a nose poke or lever press response under fixed (FUP5, FUP10, FUP25, FUP50), variable (VUP10, VUP20, VUP50), and progressive (PUP1.25, PUP1.5, PUP1.75) unit prices. Mice were run for 4 days at each cost. There were no consistent differences between the first and last day indicating that behavioral adjustments to schedule changes occurred rapidly. When averaged across all price schedules, mice in the nose poke group consumed more food than their lever press counterparts but the overall shapes of the demand curves did not differ between the two operant responses, with intake decreasing as price increased. The number of meals taken per day differed between two meal-defining criteria that we applied, and there were some differences between the types of unit price schedule. In the second experiment, approach cost in the form of nose poke responses were required to activate a response device (lever) on which a fixed unit price for food was in force. These approach and unit costs were varied systematically. Meal number decreased, and meal size increased, with increasing approach cost even though nose pokes accounted for only a small fraction of the total response activity. Thus, meal patterns in mice are sensitive to approach cost while total amount consumed is more sensitive to unit price. These data are discussed in terms of the concept of foraging cost as either a unitary or a multidimensional variable.

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“…The phenotype was reversed for transgenic mice that overexpress SERT at 2–3 fold normal levels, with a consequent decrease in brain extracellular serotonin (Jennings et al, 2006). These mice had reduced body weight and also no alteration in feeding (Pringle et al, 2008). …”

Section: Central Serotonin and Energy Balancementioning

confidence: 99%

Serotonin and the regulation of mammalian energy balance

Donovan¹,

Tecott²

2013

Front. Neurosci.

129

100

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Maintenance of energy balance requires regulation of the amount and timing of food intake. Decades of experiments utilizing pharmacological and later genetic manipulations have demonstrated the importance of serotonin signaling in this regulation. Much progress has been made in recent years in understanding how central nervous system (CNS) serotonin systems acting through a diverse array of serotonin receptors impact feeding behavior and metabolism. Particular attention has been paid to mechanisms through which serotonin impacts energy balance pathways within the hypothalamus. How upstream factors relevant to energy balance regulate the release of hypothalamic serotonin is less clear, but work addressing this issue is underway. Generally, investigation into the central serotonergic regulation of energy balance has had a predominantly “hypothalamocentric” focus, yet non-hypothalamic structures that have been implicated in energy balance regulation also receive serotonergic innervation and express multiple subtypes of serotonin receptors. Moreover, there is a growing appreciation of the diverse mechanisms through which peripheral serotonin impacts energy balance regulation. Clearly, the serotonergic regulation of energy balance is a field characterized by both rapid advances and by an extensive and diverse set of central and peripheral mechanisms yet to be delineated.

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Mice overexpressing the 5-hydroxytryptamine transporter show no alterations in feeding behaviour and increased non-feeding responses to fenfluramine

Abstract: These data suggest that overexpression of the 5-HTT does not lead to alterations in feeding or satiety in food-deprived mice but does increase the occurrence of other non-feeding behaviours in response to the 5-HT releasing agent fenfluramine.

Cited by 23 publications

References 44 publications

Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice

Opposing alterations in anxiety and species-typical behaviours in serotonin transporter overexpressor and knockout mice

Meal patterns of mice under systematically varying approach and unit costs for food in a closed economy

Serotonin and the regulation of mammalian energy balance

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