Species differences in vasopressin receptor binding are evident early in development: comparative anatomic studies in prairie and montane voles

Monogamous prairie voles (Microtus ochrogaster) and promiscuous montane voles (Microtus montanus) exhibit remarkable differences in the distribution of vasopressin (AVP) receptors in the adult brain. This difference in receptor distribution is associated with species differences in the behaviors, including pair bond formation and paternal care, found selectively in the monogamous vole. To investigate a potential mechanism for this species difference in AVP receptors, the present study examined the ontogeny of receptor binding in the two species to determine whether the adult maps arose from a shared pattern in development. By using 125I-linear-AVP, which is a selective high-affinity ligand for the V1a receptor, we found early appearance and transient expression of AVP receptor binding during postnatal development in both species. However, the ontogenetic patterns of regional AVP receptor binding were species specific. In the diagonal band, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, prairie voles had higher AVP receptor binding at birth than montane voles, and this difference persisted with little variation into adulthood. In these areas, therefore, species differences in AVP receptor binding appeared to be determined primarily by genetic or prenatal factors. In the lateral septum, both species had low levels of AVP receptor binding at birth. Thereafter, the binding increased rapidly in montane voles, but it remained unchanged in prairie voles. In the cingulate cortex, AVP receptor binding in prairie voles showed a peak in early development with a subsequent decline and reached the adult level at weaning, whereas the binding in montane voles remained unchanged into adulthood. A similar but opposite pattern was found in the frontoparietal cortex, in which AVP receptor binding showed an early peak in montane voles but did not change significantly in prairie voles. These results demonstrate that 1) species differences in regional AVP receptor binding are evident in the early postnatal period and, in several areas, may be determined by genetic or prenatal factors, and 2) AVP may target brain areas differently in infant and adult prairie and montane voles and, thus, could exert differential effects on the organization of the central nervous system in the two species of voles.     

The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster).

This study compared the effects of centrally administered oxytocin (OT) and arginine vasopressin (AVP) on partner preference formation and social contact in male and female prairie voles (Microtus ochrogaster). After 1 hr of cohabitation and pretreatment with either AVP or OT, both males and females exhibited increased social contact and significant preference for the familiar partner. After pretreatment with either an OT receptor antagonist (OTA) or an AVP (V1a) receptor antagonist (AVPA), neither OT nor AVP induced a partner preference. In addition, treatment with OT?+?OTA or AVP?+?AVPA was associated with low levels of social contact in both sexes. Either AVP or OT is sufficient to facilitate social contact if either the OT or AVP receptor is available. However, the formation of partner preferences may require access to both AVP and OT receptors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles.

The neuropeptide arginine vasopressin (AVP) modulates a variety of species-specific social behaviors. In socially monogamous male prairie voles, AVP acts centrally via vasopressin V1a receptor (V1aR) to facilitate mating induced partner preferences. The display of a partner preference requires at least 2 temporally distinct processes: social bond formation as well as its recall, or expression. Studies to date have not determined in which of these processes V1aR acts to promote partner preferences. Here, male prairie voles were administered intracerebroventricularly a V1aR antagonist (AVPA) at different time points to investigate the role of V1aR in social bond formation and expression. Animals receiving AVPA prior to cohabitation with mating or immediately prior to partner preference testing failed to display a partner preference, while animals receiving AVPA immediately after cohabitation with mating and control animals receiving vehicle at all 3 time points displayed partner preferences. These results suggest that V1aR signaling is necessary for both the formation and expression of partner preferences and that these processes are dissociable. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paternal behavior is associated with central neurohormone receptor binding patterns in meadow voles (Microtus pennsylvanicus).

Paternal and nonpaternal voles (microtus) have different arginine-vasopressin (AVP) and oxytocin (OT) receptor patterns in the extended amygdala, a neural pathway associated with parental behavior. Using receptor autoradiography, the authors examined whether AVP and OT receptor patterns were associated with facultative paternal behavior in either sexually and parentally inexperienced or experienced meadow voles (Microtus pennsylvanicus). Experienced, in contrast to inexperienced, males had less AVP binding in the lateral septum (LS), more AVP binding in the anterior olfactory nucleus (AON), and more OT binding in the AON, bed nucleus of the stria terminalis, LS, and lateral amygdala. Thus, specific AVP receptor patterns, which co-occur with paternal care in consistently paternal voles, also may be associated with paternal care (when present) in typically nonpaternal species. This study also demonstrated a possible relationship between OT receptor patterns and paternal state in male mammals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster)

After being paired with females, male prairie voles show major changes in their social behaviors among which is an increase in paternal responsiveness. These changes are accompanied by fluctuations in the density of the [Arg8]vasopressin-immunoreactive (AVP-ir) fibers in the lateral septum, suggesting that septal AVP might be involved in these changes. To explore a possible involvement of septal AVP in paternal responsiveness, we tested whether injections of saline, AVP, or the V1a receptor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),2-(O-methyltyrosine]AVP [d(CH2)5Tyr(Me)AVP] into the lateral septum influenced the four most prominent paternal activities displayed by male prairie voles; grooming, crouching over, contacting, and retrieving pups. In a first experiment, sexually inexperienced males received a single injection of AVP, saline, or d(CH2)5Tyr(Me)AVP in the lateral septum, after which their paternal responsiveness was recorded during a 10-min period. AVP-injected animals spent more time contacting and crouching over pups, while d(CH2)5Tyr(Me)AVP-injected animals spent less time grooming pups than saline-injected animals. In a follow-up study, one group of animals received an injection of AVP preceded by an injection of saline or d(CH2)5Tyr(Me)-AVP into the lateral septum. A second group of animals received an injection of saline preceded by an injection of saline or d(CH2)5Tyr(Me)AVP into the lateral septum. In both groups, animals spent less time grooming, crouching over, and contacting pups if they had first been injected with d(CH2)5Tyr(Me)AVP. Control experiments suggested that the effects of AVP on paternal responsiveness were dose- and site-specific. These data suggest that septal AVP enhances paternal responsiveness by a V1a receptor-mediated mechanism.     

A gender-specific mechanism for pair bonding: Oxytocin and partner preference formation in monogamous voles.

Previous studies have demonstrated that central administration of vasopressin but not oxytocin facilitates pair bonding in the monogamous male prairie vole. This study tested vasopressin and oxytocin in the formation of the female vole's preference for a particular male partner. Initial studies showed that in monogamous female prairie voles (but not in nonmonogamous congeners), mating was followed by a partner preference that endured for at least 2 weeks. Nonmating prairie vole females developed a partner preference following oxytocin infusions, but not after vasopressin or cerebrospinal fluid infusions. Females given a selective oxytocin antagonist showed normal mating behavior, yet failed to develop a partner preference. The vasopressin antagonist failed to block partner preference formation in mated females. These results suggest that oxytocin, released with mating, may be critical to formation of a partner preference in the female prairie vole; this contrasts to vasopressin, which appears to be more important for pair bonding in the male of this species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social investigation in a memory task relates to natural variation in septal expression of oxytocin receptor and vasopressin receptor 1a in prairie voles (Microtus ochrogaster).

Arginine vasopressin (AVP) and oxytocin (OT) influence social behavior and cognitive processes and may explain some of the variance associated with individual differences in behavior. Although great focus has been placed on the roles of these peptides in learning and memory, less attention has been given to the receptors to which they bind. The authors exposed male prairie voles (Microtus ochrogaster) to novel females in a multitrial social recognition test to investigate whether individual differences in vasopressin receptor (V1aR) or oxytocin receptor (OTR) related to social recognition. The authors also explored differences in OTR and V1aR throughout the brain to determine whether patterns of receptor coexpression emerged in functionally related structures. Male investigation of females was highly variable, and those that investigated females the most did not habituate to repeated female presentation. Moreover, high investigators expressed significantly more V1aR and less OTR in the lateral septum. Coexpression patterns of these receptors emphasize the role of OT and AVP in neural circuits involved in social behavior, reward, learning, and memory. Understanding individual differences in the laboratory may provide insight into evolved natural behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): A mechanism for pair bonding?

This study examined the role of dopamine (DA) in partner preference (PP) formation in female prairie voles (Microtus ochrogaster). The nonspecific DA antagonist haloperidol blocked mating-induced PP, whereas the nonspecific DA agonist apomorphine induced PP without mating. The D2 antagonist eticlopride, but not the D1 antagonist SCH23390, blocked PP, whereas the D2 agonist quinpirole, but not the D1 agonist SKF38393, induced PP without mating. Injections of eticlopride before or immediately after mating, but not 24 hr after mating, impaired PP, indicating that DA's effects were not due to an interference with mating or sensory recognition. Finally, intracerebroventricular (icv) injections of eticlopride diminished PP. Together, these data suggest that mating-induced PP requires activation of D2 receptors and that social experience may activate dopaminergic pathways, with enduring effects on behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster).

The prairie vole (Microtus ochrogaster), a monogamous rodent that forms long-lasting pair bonds, has proven useful for the neurobiological study of social attachment. In the laboratory, pair bonds can be assessed by testing for a partner preference, a choice test in which pair-bonded voles regularly prefer their partner to a conspecific stranger. Studies reported here investigate the role of dopamine D2-like receptors (i.e., D2, D3, and D4 receptors) in the nucleus accumbens (NAcc) for the formation of a partner preference in female voles. Mating facilitated partner preference formation and associated with an approximately 50% increase in extracellular dopamine in the NAcc. Microinjection of the D2 antagonist eticlopride into the NAcc (but not the prelimbic cortex) blocked the formation of a partner preference in mating voles, whereas the D2 agonist quinpirole facilitated formation of a partner preference in the absence of mating. Taken together, these results suggest that D2-like receptors in the NAcc are important for the mediation of social attachments in female voles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Species differences in the vasopressin-immunoreactive pathways in the bed nucleus of the stria terminalis and medial amygdaloid nucleus in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus).

Vasopressin-immunoreactive (AVP-ir) cells in the bed nucleus of the stria terminalis (BST) and medial amygdaloid nucleus (MAN) and their AVP-ir projections to the lateral septum were studied in monogamous prairie voles (Microtus ochrogaster) and promiscuous meadow voles (M. pennsylvanicus). A sexually dimorphic AVP-ir pathway was found in both species; males had more AVP-ir cells in the BST and MAN, as well as denser AVP-ir fibers in the lateral septum, than did females. A significant species difference was also found. Overall, meadow voles had more AVP-ir cells in the BST and MAN than did prairie voles. Male prairie voles, however, had a higher density of AVP-ir fibers in the lateral septum than male meadow voles. The species difference in the sexually dimorphic AVP-ir projections in the BST and MAN is implicated in the rodents' different life strategy and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in affiliative behavior, pair bonding, and vaginal cytology in two species of vole (Microtus ochrogaster and M. montanus).

Prairie voles (Microtus ochrogaster) and montane voles (M. montanus) display marked differences in social organization in the field. Trios of 1 male and 2 females were studied in a large enclosure for a 10-day period. Prairie voles spent 59% of the observation time in side-by-side contact, whereas montane voles spent only 7% of the time in contact. Vaginal smears indicated female–female suppression of estrus in prairie voles; female montane voles appeared to cycle in the presence of males. Male prairie voles preferentially paired and nested with 1 of the females, and vaginal estrus generally followed pair formation by 2 days. Male montane voles did not spend time preferentially with either female, even after mating. These results suggest that the contrasting mating systems of these species result from differences in the propensity for affiliative behavior and social bonding rather than from mate availability or female receptivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developmental exposure to oxytocin facilitates partner preferences in male prairie voles (Microtus ochrogaster).

The authors investigated the effects of postnatal manipulations of oxytocin (OT) on the subsequent tendency to form a partner preference in male prairie voles (Microtus ochrogaster). Neonatally, males received either an injection of OT, an oxytocin antagonist (OTA), 0.9% saline vehicle, or handling without injection. As adults, males were tested for partner preference following 1 hr of cohabitation with a nonestrous female. In a 3-hr preference test, males neonatally exposed to exogenous OT exhibited a significant partner preference, not seen in males receiving OTA or saline. Both OT and OTA voles had significantly higher levels of social contact than saline controls. A single neonatal injection of OT increased both total and selective social behaviors in male prairie voles. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.     

Three experiments on mate choice in meadow voles (Microtus pennsylvanicus).

Species differences in selectivity with respect to mate choice have been hypothesized to be related to mating systems. Procedures used in 3 previous experiments on monogamous prairie voles (Microtus ochrogaster) and polygamous montane voles (M. montanus) were used with polygamous meadow voles (M. pennsylvanicus). The expectation was that meadow voles would show few preferences. Female meadow voles preferred mating with familiar versus unfamiliar males but displayed no preference for unmated versus mated males. Male meadow voles displayed no preference for unmated versus mated females. The results are partially consistent with the hypothesis that relates mate choice to social and mating system, as this polygamous species resembles polygamous montane voles species in 2 situations but is similar to monogamous prairie voles in the 3rd. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Copulatory behavior of voles (Microtus montanus and M. ochrogaster) in multiple-female test situations.

12 male prairie voles and 12 male mountain voles were given test of copulatory behavior with 1, 2, or 4 mating partners. Changes in the number of available partners produced minimal changes in the parameters of copulatory behavior in males of the 2 species. Male montane voles generally copulated with more of the females, showed a lesser tendency to concentrate copulations on a single female, and changed females more often than did prairie voles. These differences are consistent with differences in social structure reported in field studies and may reflect processes underlying species differences in social organization. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Actual standards for drinking water quality

In freshly isolated rat CCD segments, the effects of arginine vasopressin (AVP), oxytocin (OT), adrenaline (Ad), and their specific receptor agonists and antagonists on the intracellular Ca2+ activity ([Ca2+]i) were measured using the Ca2+ sensitive dye Fura-2 as fluorescence indicator. We observed that AVP, the V1-receptor agonist [Phe2Orn8] vasotocin ([Phe2]OVT), and OT increased [Ca2+]i biphasically. AVP (n = 9) and OT (n = 8) induced increases in [Ca2+]i were completely blocked by the V1A-receptor antagonist d(CH2)5Tyr(Me)2AVP. However, neither the V2-receptor agonist [Val4-D-Arg8]AVP (100 nM, n = 5), nor the OT-receptor agonist [Thr4,Gly7]OT (100 nM, n = 5) nor forskolin (1 microM, n = 4 and 10 microM, n = 5) did significantly change [Ca2+]i. Ad and the beta-adrenoceptor agonist isoproterenol (ISO) increased [Ca2+]i, which was not mimicked by the alpha 2-adrenoceptor agonist clonidine (1 microM, n = 10) or the alpha 1-adrenoceptor agonist phenylephrine (1 microM, n = 5). The beta-adrenoceptor antagonist propranolol (1 microM) completely blocked this Ad (1 microM, n = 4) induced [Ca2+]i increase. Insulin (INS 10 nM, n = 8), endothelin (ET 1 microM, n = 6), and angiotensin II (Ang II 1 pM to 10 nM; each n = 4) had no significant effect on [Ca2+]i. Considering the present results we propose a V1A-receptor and beta-adrenoceptor dependent modulation of [Ca2+]i in rat CCD.     

Acts, omissions, intentions and motives: a philosophical examination of the moral distinction between killing and letting die

1. The exact nature of the receptor subtype(s) involved in the action of arg-vasopressin (AVP) on the rat aorta and small mesenteric artery (SMA) is controversial. Therefore, we have studied the effects of the selective V1A receptor antagonists, OPC 21268 and SR 49059, and the oxytocin (OT) receptor antagonist, atosiban, on the AVP- and OT-induced contractions of the two vessels. 2. AVP and OT displayed similar intrinsic activities in the rat aorta and SMA, but AVP was approximately 130 fold and approximately 500 fold more potent than OT, respectively. In the rat aorta, Hill slopes (nH) were similar for OT and AVP. However, in rat SMA, the OT concentration-effect (E/[A]) curve was significantly steeper than the AVP E/[A] curve (nH, = 3.3+/-0.20, 2.3+/-0.15; P<0.001). 3. In the aorta OPC 21268, SR 49059 and atosiban competitively antagonized the AVP and OT E/[A] curves. Except for atosiban and SR 49059 against AVP, competitive antagonism was also observed in the SMA. Atosiban caused concentration-dependent steepening of the AVP E/[A] curve, whereas SR 49059 decreased the upper asymptote. 4. Schild analysis yielded affinities indicative of V1A receptor involvement in both vessels: pKB/ pA2=9.20 9.48, 7.56 7.71 and 6.19 6.48 for SR 49059, OPC 21268 and atosiban, respectively. 5. Neither AVP nor OT relaxed U46619 pre-contracted aorta or SMA in the presence of SR 49059, suggesting no interference of a vasodilatory component. 6. Despite predominant involvement of V1A receptors in both vessels, the different Hill slopes of AVP and OT E/[A] curves as well as the steepening of the AVP E/[A] curves by atosiban are indicative of receptor heterogeneity in the rat SMA.     

Day length and sociosexual cohabitation alter central oxytocin receptor binding in female meadow voles (Microtus pennsylvanicus).

Nonmonogamous meadow voles, which exhibit seasonal changes in social organization (long day [LD] females are territorial, short day [SD] females live socially), provide a model for examining whether central oxytocin (OT) receptor patterns are associated with seasonal changes in intraspecific social behaviors. This study examined whether sexually inexperienced (naive) SD females had more OT receptor binding than naive LD females. Naive SD females had greater OT receptor binding in the lateral septum (LS), lateral amygdala (LatAmyg), and central amygdala, (CenAmyg) than less social, naive LD females. Because both SD and LD females acquire partner preferences, the association of OT receptor binding with partner preference onset was assessed. For LD females, partner preference onset corresponded with greater OT receptor binding in the anterior olfactory nucleus, LS, and bed nucleus of the stria terminalis, compared with naive LD females. Naive SD females and those exhibiting partner preferences did not differ, but those that failed to acquire partner preferences showed less OT binding in the LatAmyg and CenAmyg. Results show that OT receptor patterns are associated with seasonal changes in intraspecific social organization and partner preference onset in a nonmonogamous rodent. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Severe loss of vasopressin-immunoreactive cells in the suprachiasmatic nucleus of aging voles coincides with reduced circadian organization of running wheel activity

Aging leads to a decrease in circadian organization of behavior. Whether this general observation is related to the finding that in older subjects the arginine-vasopressin (AVP) system in the suprachiasmatic nucleus (SCN) has deteriorated is an unsolved question. Here we assessed circadian organization of running wheel behavior and numbers of AVP cells in the SCN of old voles (n=12, 11. 5 months of age) and compared the results with data from young voles (n=16, 4.5 months of age). A third of the young voles, but three-quarter of the old voles lost circadian rhythmicity. Analysis of daily onset to onset periodicity of running wheel activity at the age of 5 and 10 months in individual voles revealed a significant loss of precision of circadian rhythmicity at the higher age. The number of AVP cells in the SCN of old voles decreased substantially, over 78% compared to young voles in general. AVP cell numbers, however, cannot be directly correlated with the state of rhythmicity in old voles; in one of the three circadian rhythmic old voles the SCN contained the least AVP cells. This study does not support the idea of a causal relationship between aging induced reduction in AVP cells in the SCN and the presence of circadian rhythmicity in behavior.     

Dopamine Antagonists Do Not Block Conditioned Place Preference Induced by Paced Mating Behavior in Female Rats.

The authors assessed the behavioral effects of dopamine (DA) receptor antagonists, Cis (Z) flupentixol and S(+)-raclopride L-tartrate, on conditioned place preference (CPP) induced by paced mating behavior. Ovariectomized female rats of the Wistar strain were used. The administration of amphetamine (1 ior. mg/kg) induced a clear CPP that was completely blocked by the DA antagonists flupentixol (0.25 mg/kg) or raclopride (0.125 mg/kg). These doses had no effect on motor coordination. Female rats that mated in a pacing chamber developed a clear CPP. Neither flupentixol nor raclopride blocked the reward state induced by paced mating behavior. These results indicate that DA is not involved in the reward state induced by paced mating behavior in female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)