V1a receptor knockout mice exhibit impairment of spatial memory in an eight-arm radial maze

Egashira, Nobuaki; Tanoue, Akito; Higashihara, Fuminori; Mishima, Kenichi; Fukue, Yoshihiko; Takáno, Yukio; Tsujimoto, Gozoh; Iwasaki, Katsunori; Fujiwara, Michihiro

doi:10.1016/j.neulet.2003.11.050

Cited by 62 publications

(43 citation statements)

References 22 publications

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“…The V 1a receptor was recently reported to play a major role in spatial memory (37), heart hypertrophy (38), and hyperfiltration (39). Selective inhibition of this receptor subtype may therefore have important therapeutic applications.…”

Section: Discussionmentioning

confidence: 99%

Conopressin-T from Conus tulipa Reveals an Antagonist Switch in Vasopressin-like Peptides

Dutertre

Croker²,

Daly

et al. 2008

Journal of Biological Chemistry

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We report the discovery of conopressin-T, a novel bioactive peptide isolated from Conus tulipa venom. Conopressin-T belongs to the vasopressin-like peptide family and displays high sequence homology to the mammalian hormone oxytocin (OT) and to vasotocin, the endogenous vasopressin analogue found in teleost fish, the cone snail's prey. Conopressin-T was found to act as a selective antagonist at the human V 1a receptor. All peptides in this family contain two conserved amino acids within the exocyclic tripeptide (Pro 7 and Gly 9 ), which are replaced with Leu 7 and Val 9 in conopressin-T. Whereas conopressin-T binds only to OT and V 1a receptors, an L7P analogue had increased affinity for the V 1a receptor and weak V 2 receptor binding. Surprisingly, replacing Gly 9 with Val 9 in OT and vasopressin revealed that this position can function as an agonist/antagonist switch at the V 1a receptor. NMR structures of both conopressin-T and L7P analogue revealed a marked difference in the orientation of the exocyclic tripeptide that may serve as templates for the design of novel ligands with enhanced affinity for the V 1a receptor.The vasopressin (AVP) 3 and oxytocin (OT) peptides were originally discovered and identified as neurohypophysial hormones in mammals (1). In humans, AVP acts via three vasopressin receptors (vascular V 1a R, pituitary V 1b R, and renal V 2 R), whereas OT acts via one OT receptor (OTR). All targets are members of the G protein-coupled receptor family (2). Peripherally, they regulate water balance, the control of blood pressure, and contraction of uterine smooth muscle and mammary myoepithelium (3). Centrally, these peptides affect levels of aggression, depression, and young parent bonding (4 -6). Endogenous analogues of OT and AVP have been reported in nonmammalian vertebrates, annelids, molluscs, and insects, suggesting an old lineage for these peptides (7). Surprisingly, two variants were also found in the venom of predatory cone snails. The original discovery of these two AVP analogues, named conopressins, was based on the characteristic "scratching" effect observed upon intracerebral injection into mice (8). Although the sequences of conopressins are similar to vasopressin itself, they have an additional positive charge in position 4, which is only found in two other endogenous vasopressin analogues, cephalotocin (Octopus vulgaris) and annetocin (Eisenia foetida). Conopressin-S was isolated from Conus striatus, whereas conopressin-G was first isolated from Conus geographus venom but later found in Conus imperialis venom as well as in tissue extracts of the nonvenomous snails Lymnea stagnalis and Aplysia californica and the leech Erpobdella octoculata (9 -11).Molluscs of the genus Conus produce bioactive peptides in a combinatorial fashion. As demonstrated for the snake toxins (12), most conotoxins or conopeptides are believed to be derived from an endogenous structural template (13). Because conopressin-G is widely distributed, it may represent the endogenous hormone in Gastropods and Annelid...

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Section: Discussionmentioning

confidence: 99%

Conopressin-T from Conus tulipa Reveals an Antagonist Switch in Vasopressin-like Peptides

Dutertre

Croker²,

Daly

et al. 2008

Journal of Biological Chemistry

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“…Orexin/EGFP mice (Yamanaka et al, 2003a,b) were used for whole-cell recordings. The V1aR Ϫ/Ϫ mice (Egashira et al, 2004) were maintained on a mixed genetic background (129sv:C57Black/6J ϭ 1:1). V1aR Ϫ/Ϫ mice were crossed with orexin/EGFP mice to obtain V1aR Ϫ/Ϫ ; orexin/EGFP mice.…”

Section: Methodsmentioning

confidence: 99%

“…Recent studies using knock-out mice have begun to reveal the physiological role of AVP and oxytocin in the CNS. V1a receptor knock-out (V1aR Ϫ/Ϫ ) mice showed abnormalities in spatial memory (Egashira et al, 2004), social interaction and anxiety (Bielsky et al, 2005;Egashira et al, 2007), and metabolism (Hiroyama et al, 2007). Oxytocin knock-out mice revealed that oxytocin plays an important role in social cognition and social, sexual, and maternal behavior (Winslow and Insel, 2002).…”

Section: Introductionmentioning

confidence: 99%

Vasopressin Increases Locomotion through a V1a Receptor in Orexin/Hypocretin Neurons: Implications for Water Homeostasis

Tsunematsu¹,

Fu²,

Yamanaka³

et al. 2008

J. Neurosci.

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Water homeostasis is a critical challenge to survival for land mammals. Mice display increased locomotor activity when dehydrated, a behavior that improves the likelihood of locating new sources of water and simultaneously places additional demands on compromised hydration levels. The neurophysiology underlying this well known behavior has not been previously elucidated. We report that the anti-diuretic hormone arginine-vasopressin (AVP) is involved in this response. AVP and oxytocin directly induced depolarization and an inward current in orexin/hypocretin neurons. AVP-induced activation of orexin neurons was inhibited by a V1a receptor (V1aR)-selective antagonist and was not observed in V1aR knock-out mice, suggesting an involvement of V1aR. Subsequently activation of phospholipase C␤ triggers an increase in intracellular calcium by both calcium influx through nonselective cation channels and calcium release from calcium stores in orexin neurons. Intracerebroventricular injection of AVP or water deprivation increased locomotor activity in wild-type mice, but not in transgenic mice lacking orexin neurons. V1aR knock-out mice were less active than wild-type mice. These results suggest that the activation of orexin neurons by AVP or oxytocin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a key role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature.

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“…A different KO line of the Avpr1a demonstrates a lower basal blood pressure (Egashira et al, 2004;Koshimizu et al, 2006) and impaired lipid metabolism and glucose homeostasis Hiroyama et al, 2007). Both lines have changes in behavior as discussed below.…”

Section: Gene Inactivation In Micementioning

confidence: 99%

“…Injection of an Avpr1a antagonist suppressed the NC-1900 improvement on scopolamine-induced spatial memory deficits (Mishima et al, 2003), contrary to prior studies in which an Avpr1a antagonist did not impair performance on the radial arm maze (Dietrich and Allen, 1997a) or the Morris water maze (Everts and Koolhaas, 1999), in which an animal is trained to swim to a hidden escape platform using extra-maze spatial cues. However, Avpr1a KO mice have impaired working memory in the radial arm maze as compared to controls (Egashira et al, 2004;Egashira et al, 2006), indicating a role for the Avpr1a receptor in spatial task performance. Conversely, Avpr1b KO mice do not have impaired spatial memory on the Morris water maze (Wersinger et al, 2002;Egashira et al, 2004).…”

Section: Spatial Learningmentioning

confidence: 99%

Vasopressin: Behavioral roles of an “original” neuropeptide

Caldwell

Lee

Macbeth

et al. 2008

Progress in Neurobiology

419

416

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Vasopressin (Avp) is mainly synthesized in the magnocellular cells of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) whose axons project to the posterior pituitary. Avp is then released into the blood stream upon appropriate stimulation (e.g., hemorrhage or dehydration) to act at the kidneys and blood vessels. The brain also contains several populations of smaller, parvocellular neurons whose projections remain within the brain. These populations are located within the PVN, bed nucleus of the stria terminalis (BNST), medial amygdala (MeA) and suprachiasmatic nucleus (SCN).Since the 1950's, research examining the roles of Avp in the brain and periphery has intensified. The development of specific agonists and antagonists for Avp receptors has allowed for a better elucidation of its contributions to physiology and behavior. Anatomical, pharmacological and transgenic, including "knockout," animal studies, have implicated Avp in the regulation of various social behaviors across species.Avp plays a prominent role in the regulation of aggression, generally of facilitating or promoting it. Affiliation and certain aspects of pair-bonding are also influenced by Avp. Memory, one of the first brain functions of Avp that was investigated, has been implicated especially strongly in social recognition. The roles of Avp in stress, anxiety, and depressive states are areas of active exploration. In this review, we concentrate on the scientific progress that has been made on understanding the role of Avp in regulating of these and other behaviors across species, as well as discuss the implications for human behavior.

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V1a receptor knockout mice exhibit impairment of spatial memory in an eight-arm radial maze

Cited by 62 publications

References 22 publications

Conopressin-T from Conus tulipa Reveals an Antagonist Switch in Vasopressin-like Peptides

Conopressin-T from Conus tulipa Reveals an Antagonist Switch in Vasopressin-like Peptides

Vasopressin Increases Locomotion through a V1a Receptor in Orexin/Hypocretin Neurons: Implications for Water Homeostasis

Vasopressin: Behavioral roles of an “original” neuropeptide

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