Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions

Simon, Patricia; Dupuis, Reynald; Costentin, Jean

doi:10.1016/0166-4328(94)90008-6

Cited by 624 publications

(435 citation statements)

References 14 publications

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“…The mechanism of behavioral activation in KO mice is quite different from that of psychostimulant-induced stereotypies. Psychostimulants at high doses induce hyperlocomotion and thigmotaxis in the OF (Simon et al, 1994) by eliciting a massive DA release in the basal ganglia of normal rodents (Kuczenski and Segal, 1997). Interestingly, tissues contents of DA and 5-HT are reduced under basal conditions in frontal cortex, dorsal striatum, and ventral striatum of KO mice.…”

Section: Discussionmentioning

confidence: 98%

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Pogorelov

Rodriguiz

Insco

et al. 2005

Neuropsychopharmacol

136

116

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Disruption of the dopamine (DA) transporter (Dat1) gene in mice leads to a 50% reduction or complete elimination of Dat1 expression in striatum of respective heterozygous (HZ) and knockout (KO) mice. Compared to wild-type (WT) controls, extracellular DA is increased approximately two-and five-fold in the mutants. Although open field (OF) activity is similar for WT and HZ animals, it is enhanced for KO mice. The purpose of the present investigations was to study spontaneously emitted behaviors and to determine the behavioral and neurochemical mechanisms that may contribute to the hyperactivity of KO animals. Heterozygotes are less anxious than other genotypes and they engage in novelty-seeking behaviors that include increased time spent in the center of the OF, enhanced investigation of objects, and augmented free exploration of a novel environment. By comparison, KO mice display neophobia when initially exposed to novel conditions. Over time the anxiety-like response habituates and behaviors become activated and stereotyped; these responses are unrelated to exploration or novelty seeking. No alterations in extracellular DA levels or tissue contents from several brain regions are detected at the time of stereotypic activation of KO mice. By contrast, this behavior is accompanied by changes in serotonin metabolism in basal ganglia. This feature may contribute to the behavioral inflexibility of KO mice in different experimental contexts. Collectively, these findings suggest that disruption of the Dat1 gene in mice leads to two different phenotypes; one related to anxiety-reducing and novelty seeking, while the other has some homology to disorders with a stereotypical-perseverative spectrum.

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Section: Discussionmentioning

confidence: 98%

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Pogorelov

Rodriguiz

Insco

et al. 2005

Neuropsychopharmacol

136

116

View full text Add to dashboard Cite

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“…3G). AKAP220-KO mice traveled only 7.3 ± 0.5 m (n = 8) over the 30-min period, whereas the WT mice traveled a total distance of 11.3 ± 0.6 m (n = 8; Open-field testing can reveal basic anxiety behaviors such as thigmotaxis, a tendency to remain close to the walls rather than exploring the open central zone of the arena (36). AKAP220-KO mice made significantly fewer excursions into the central zone during the 30-min trial (90.3 ± 9 entries; n = 8) compared with WT (139 ± 9.7 entries; n = 8; Fig.…”

Section: Resultsmentioning

confidence: 99%

AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

Whiting

Ogier

Forbush

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an "actin barrier" that obstructs the passive transit of AQP2 to the plasma membrane. Bidirectional control of AQP2 trafficking is managed by hormones and signaling enzymes. We have discovered that vasopressin-independent facets of this homeostatic mechanism are under the control of A-Kinase Anchoring Protein 220 (AKAP220; product of the Akap11 gene). CRISPR/Cas9 gene editing and imaging approaches show that loss of AKAP220 disrupts apical actin networks in organoid cultures. Similar defects are evident in tissue sections from AKAP220-KO mice. Biochemical analysis of AKAP220-null kidney extracts detected reduced levels of active RhoA GTPase, a well-known modulator of the actin cytoskeleton. Fluorescent imaging of kidney sections from these genetically modified mice revealed that RhoA and AQP2 accumulate at the apical surface of the collecting duct. Consequently, these animals are unable to appropriately dilute urine in response to overhydration. We propose that membrane-proximal signaling complexes constrained by AKAP220 impact the actin barrier dynamics and AQP2 trafficking to ensure water homeostasis. yet only approximately 1.5 L of urine is excreted. The majority of this water is reabsorbed from the luminal fluid of the nephron (1). Regulated water reabsorption in response to dehydration occurs through aquaporin-2 (AQP2) water pores in the principal cells of the collecting duct (2). This is stimulated by the hormone arginine vasopressin (AVP). Vasopressin induces PKA phosphorylation of serine 256 on AQP2 and stimulates its translocation from intracellular vesicles to the apical membranes of cells lining the collecting ducts. Reabsorption of water through the kidney preserves fluid balance and results in more concentrated urine (3, 4). Conversely, when an animal ingests excess water, decreased plasma osmolality inhibits vasopressin release, and AQP2 is recovered from the apical membrane by endocytosis. This renders the collecting duct impermeable to water, thereby diverting excess water through the ureter to the bladder.Not surprisingly, defects in AQP2 trafficking have pathophysiological outcomes. For example, nephrogenic diabetes insipidus (NDI) is associated with impaired vasopressin signaling to AQP2 (5-8). Symptoms include excessive thirst, excretion of a large volume of dilute urine, and electrolyte imbalances, including hypernatremia (1, 5). Hereditary forms of this disease appear in patients with inactivating mutations in the V2 vasopressin receptor (V2R) or AQP2 (9-12). Thus, understanding the molecular mechanisms that govern bidirectional control of AQP2 location may lead to new therapeutic approaches for the treatment of NDI.Although the enzymes and effector proteins that govern AQP2 in...

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“…In fact, slow learners showed high levels of thigmotactic swimming, which is characterized by navigating in circles and interferes with the development of an active searching strategy to find the escaping platform. Interestingly, such a thigmotactic behavior could reflect high anxiety levels in slow learners (Simon et al 1994), which, in turn, might interfere with an effective task acquisition (McNaughton 1997). It is also interesting to note that a lack of correlation between PSA cell number and swim time was observed in passive controls (which swim for the same time as trained rats) and in animals rendered amnesic by scopolamine injections, at the 12-h time point (Fig.…”

Section: Learning and Memory 247mentioning

confidence: 93%

Neurobiological and Endocrine Correlates of Individual Differences in Spatial Learning Ability

Sandi¹,

Cordero²,

Merino³

et al. 2004

Learn. Mem.

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The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former.

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Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions

Cited by 624 publications

References 14 publications

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

Novelty Seeking and Stereotypic Activation of Behavior in Mice with Disruption of the Dat1 Gene

AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

Neurobiological and Endocrine Correlates of Individual Differences in Spatial Learning Ability

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