Local vasotocin modulation of the pacemaker nucleus resembles distinct electric behaviors in two species of weakly electric fish.

The neural bases of social behavior diversity in vertebrates have evolved in close association with hypothalamic neuropeptides. In particular, arginine-vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Behavioral displays in weakly electric fish are channeled through specific patterns in their electric organ discharges (EODs), whose rate is ultimately controlled by a medullary pacemaker nucleus (PN). We first explored interspecific differences in the role of AVT as modulator of electric behavior in terms of EOD rate between the solitary Gymnotus omarorum and the gregarious Brachyhypopomus gauderio. In both species, AVT IP injection (10µg/gbw) caused a progressive increase of EOD rate of about 30%, which was persistent in B. gauderio, and attenuated after 30min in G. omarorum. Secondly, we demonstrated by in vitro electrophysiological experiments that these behavioral differences can be accounted by dissimilar effects of AVT upon the PN in itself. AVT administration (1µM) to the perfusion bath of brainstem slices containing the PN produced a small and transient increase of PN activity rate in G. omarorum vs the larger and persistent increase previously reported in B. gauderio. We also identified AVT neurons, for the first time in electric fish, using immunohistochemistry techniques and confirmed the presence of hindbrain AVT projections close to the PN that might constitute the anatomical substrate for AVT influences on PN activity. Taken together, our data reinforce the view of the PN as an extremely plastic medullary central pattern generator that not only responds to higher influences to adapt its function to diverse contexts, but also is able to intrinsically shape its response to neuropeptide actions, thus adding a hindbrain target level to the complexity of the global integration of central neuromodulation of electric behavior.

Vasotocinergic and isotocinergic systems in the gilthead sea bream (Sparus aurata): an osmoregulatory story.

To investigate the physiological roles of arginine vasotocin (AVT) and isotocin (IT) in osmoregulatory process in gilthead sea bream (Sparus aurata), a time course study (0, 12h, and 1, 3, 7 and 14 days) has been performed in specimens submitted to hypoosmotic (from 40‰ salinity to 5‰ salinity) or hyperosmotic (from 40‰ salinity to 55‰ salinity) challenges. Plasma and liver osmoregulatory and metabolic parameters, as well as AVT and IT pituitary contents were determined concomitantly with hypothalamic pro-vasotocin (pro-VT) and pro-isotocin (pro-IT) mRNA expression levels. Previously, sequences coding for pro-VT and pro-IT cDNAs were cloned. Two osmoregulatory periods related to plasma osmolality and metabolic parameter variations could be distinguished: i) an adaptative period, from 12h to 3 days after transfer, and ii) a chronic regulatory period, starting at day 3 after transfer. Higher values in hypothalamic pro-VT and pro-IT mRNA expression as well as in pituitary AVT and IT storage levels in both hypo- and/or hyper-osmotic transfers have been distinguished. These increase correlated with changes in plasma cortisol levels, suggesting an interaction between this hormone and pro-VT expression. Furthermore, pro-IT expression enhancement also suggests a role of the isotocinergic system as a modulator in the acute stress response induced by hyper-osmotic challenge in S. aurata.

Early embryonic administration of xenoestrogens alters vasotocin system and male sexual behavior of the Japanese quail.

The copulatory behavior and the parvocellular vasotocin (VT) system of the nucleus of the stria terminalis (BST) are sexually dimorphic in the Japanese quail. Embryonic administration of estradiol benzoate (EB) induces an organizational effect determining the disappearance of such a dimorphism (male shows behavior and cerebral phenotype of the female). The VT parvocellular system can therefore be considered an accurate marker of the sexual differentiation of brain circuits and a very sensitive indicator of the activity of estrogen-like substances on neural circuits. To test this hypothesis we administered diethylstilbestrol (DES), a powerful synthetic xenoestrogen, genistein (GEN), a phytoestrogen produced by soy, and bisphenol A (BPA). After 3 days of incubation, quail eggs were injected with vehicle, EB, DES, GEN or BPA. Administration of BPA caused an early blockage of development and no further analyses were done on the BPA groups. At puberty, the copulatory behavior of EB- or DES-treated male quail was totally abolished, whereas only the highest doses of GEN determined a significant decrease of the behavior. After the tests, the animals were sacrificed and perfused. The fractional area (FA) covered by VT immunoreactivity was analyzed in BST, medial preoptic nucleus, and lateral septum by computerized image analysis. The FA was significantly reduced after treatment with EB, DES and GEN at high doses. These results confirm that the sexually dimorphic VT system of the Japanese quail is a sensible indicator of the effects of xenoestrogens at the level of the central nervous system.

Vasotocin treatment inhibits courtship in male zebra finches; concomitant androgen treatment inhibits this effect.

Zebra finches evolved in arid areas of Australia. Their reproduction is stimulated by water availability, which is unpredictable. Cheng (Poult. Sci. Rev. 5 (1993) 37) hypothesized that the primary mechanism controlling reproduction in species relying on unpredictable cues should be inhibitory. The onset of stimulatory environmental conditions terminates the inhibition, allowing rapid initiation of reproduction. As the primary hormone regulating water balance in birds, arginine vasotocin (AVT) appears a likely candidate to modulate reproduction in finches. Drought conditions cause sustained AVT release, which in other species inhibits androgen production. To determine whether increased AVT inhibits reproductive behavior, intact males were tested with females and divided into three groups matched for courtship behavior. Osmotic minipumps containing (a) saline, (b) 264 ng AVT, or (c) 1320 ng AVT in saline were implanted subcutaneously and males tested 48 h later. AVT-treated males socialized with females, but the high dose significantly reduced singing and courtship displays. To determine whether AVT acted by depressing androgen secretion, additional males were given subcutaneous androgen implants and divided into two groups matched for courtship behavior. Males were then implanted with minipumps containing (a) saline or (b) the high AVT dose. Males treated with AVT plus androgen showed no deficits in courtship behavior. These data suggest that AVT secretion during periods of drought may inhibit reproduction by inhibiting androgen production. Inhibition of reproductive behavior by AVT may be a more general phenomenon. Large quantities of AVT or, in mammals the closely-related peptide vasopressin (VP), are released when animals are stressed, and high levels of AVT/VP may inhibit reproductive behavior. The extremely short half-life of these peptides means that once proximal factors become more favorable, the gonads should rapidly be released from the peptides' inhibitory actions.

Something fishy in the rat brain: molecular genetics of the hypothalamo-neurohypophysial system.

The brain peptides vasopressin and oxytocin play crucial roles in the regulation of salt and water balance. The genes encoding these neurohormones are regulated by cell-specific and physiological cues, but the molecular mechanisms remain obscure. New strategies, involving the introduction of rat transgenes into rats, are being used to address these issues, but the complexity of the rat genome has hampered progress. By contrast, the pufferfish, Fugu rubripes, has a "junk-free" genome. The oxytocin homologue from Fugu, isotocin, has been introduced into rats and is expressed in oxytocin neurons, where it is upregulated by physiological perturbations that upregulate the oxytocin gene. The Fugu and rat lineages separated 400 million years ago, yet the mechanisms that regulate the isotocin and oxytocin genes have been conserved. Fugu genome analysis and transgenesis in the physiologically tractable rat host are a powerful combination that will enable the identification of fundamental components of the neural systems that control homeostasis.

The pineal gland: anatomy, physiology, and clinical significance.

Since the discovery of melatonin approximately 25 years ago, there has been intense study regarding the details of the structure and function of the pineal gland. This work is reviewed, with particular emphasis on those aspects of importance to human physiology and disease.

Arginine vasotocin as a pineal hormone.

The pineal nonapeptide hormone arginine vasotocin (AVT) is synthesized by the ependymal cells of the pineal recess and subcommissural organ and stored in so far undefined cells of the pineal gland proper. AVT is first released into the cerebrospinal fluid (CSF) and reaches the blood only secondarily after its absorption from CSF. It displays a diurnal rhythm in the pineal and CSF, suggesting its release into the CSF during the night in the dark. Melatonin represents its releasing hormone. AVT exerts both its endocrine and non-endocrine effects by a unique mechanism involving the activation of serotonin neurotransmission in the brain with resultant inhibition of release of hypothalamic releasing and inhibiting hormones and induction of sleep. It produces both its endocrine effects and sleep at concentrations equivalent to only several hundreds of molecules, being thus by far the most active hormone so far known. Midbrain raphe nuclei or some structures intimately correlated with these cell bodies, most contain the extremely sensitive and specific AVT receptors in the mammalian brain. In contrast with its natural analogues arginine vasopressin and oxytocin which are mainly blood hormones, AVT is a CSF hormone whose major if not the sole site of action is the brain itself.