Central vasopressin pathways have been implicated in the mediation of paternal behavior, selective aggression, and affiliation in monogamous prairie voles. Here we demonstrate markedly different patterns of brain vasopressin receptor binding in the monogamous prairie vole and the congeneric nonmonogamous (promiscuous) montane vole. Vasopressin binding was assessed with both 3H-vasopressin and 125I-sarc-AVP using receptor autoradiography. The specificity of binding was consistent with a V1a receptor, the saturation kinetics were similar in the two species, and neither species showed evidence of sexual dimorphisms. In the prairie vole, highest specific binding was observed in the accessory olfactory bulb, diagonal band, laterodorsal thalamus, and superior colliculus. In the montane vole, specific binding was observed in the accessory olfactory bulb and superior colliculus as well, but in several other regions with high levels of binding in the prairie vole, binding was low or undetectable in the montane vole. In this nonmonogamous species, specific binding was high in lateral septum. Functional studies demonstrated the induction of phosphoinositol by AVP in the septum of the montane vole but not in the prairie vole. The pattern of 125I-sarc-AVP binding to lateral septum may reflect the social organization of these two species, as similar differences in AVP receptor distribution in the lateral septum were also observed in two related species, pine voles and meadow voles, which are monogamous and nonmonogamous, respectively. These results, along with earlier studies of AVP's effects on pair bonding, suggest the importance of this neuropeptide for the mediation of behaviors related to social organization.
Studies in several species of rodents show that arginine vasopressin (AVP) acting through a V 1A receptor facilitates offensive aggression, i.e., the initiation of attacks and bites, whereas serotonin (5-HT) acting through a 5-HT 1B receptor inhibits aggressive responding. One area of the CNS that seems critical for the organization of aggressive behavior is the basolateral hypothalamus, particularly the anterior hypothalamic region. The present studies examine the neuroanatomical and neurochemical interaction between AVP and 5-HT at the level of the anterior hypothalamus (AH) in the control of offensive aggression in Syrian golden hamsters. First, specific V 1A and 5-HT 1B binding sites in the AH are shown by in vitro receptor autoradiography. The binding for each neurotransmitter colocalizes with a dense field of immunoreactive AVP and 5-HT fibers and putative terminals. Putative 5-HT synapses on AVP neurons in the area of the AH are identified by double-staining immunocytochemistry and laser scanning confocal microscopy. These morphological data predispose a functional interaction between AVP and 5-HT at the level of the AH. When tested for offensive aggression in a resident /intruder paradigm, resident hamsters treated with fluoxetine, a selective 5-HT reuptake inhibitor, have significantly longer latencies to bite and bite fewer times than vehicle-treated controls. Conversely, AVP microinjections into the AH significantly shorten the latency to bite and increase biting attacks. The action of microinjected AVP to increase offensive aggression is blocked by the pretreatment of hamsters with fluoxetine. These data suggest that 5-HT inhibits fighting, in part, by antagonizing the aggressionpromoting action of the AVP system. Two neurotransmitter systems implicated in the control of aggressive behavior are arginine vasopressin (AVP) and serotonin (5-HT). AVP is a neurochemical signal affecting numerous brain functions (DeWied, 1971;Cooper et al., 1979;Pittman et al., 1982;Fehm-Wolfsdorf et al., 1988;Dantzer and Bluthe, 1992), including aggression (Ferris and Potegal, 1988, Koolhaas et al., 1990Potegal and Ferris, 1990;Winslow et al., 1993; Delville et al., 1996a,b). For example, microinjection of AVP V 1A -receptor antagonist into the anterior hypothalamus (AH) of a hamster causes a dose-dependent inhibition of offensive aggression, i.e., initiated attacks and bites toward a conspecific placed into their home cage (Ferris and Potegal, 1988). Similarly, AVP receptor blockade in the AH significantly reduces aggression between hamsters paired together in a neutral arena .Although AVP facilitates offensive aggression, 5-HT is reported to have the opposite effect and diminishes aggressive behavior (for review, see Olivier and Mos, 1990). For example, rats show an increase in offensive aggression after treatment with neurotoxins that deplete 5-HT levels in the hypothalamus (Vergnes et al., 1988). Conversely, rats treated with eltoprazine, a 5-HT 1 receptor agonist, show a dose-dependent decrease in offensive aggressi...
Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 +/- 0.25 and 1.27 +/- 0.29 mL. g-1. min-1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased Pco(2) and Po(2). During 5% CO(2) challenge, under awake and anesthetized conditions, respectively, CBF increased 51 +/- 11% and 25 +/- 4%, and BOLD increased 7.3 +/- 0.7% and 5.4 +/- 0.4%. During 10% CO(2) challenge, CBF increased 158 +/- 28% and 47 +/- 11%, and BOLD increased 12.5 +/- 0.9% and 7.2 +/- 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.
Functional magnetic resonance imaging (fMRI) in conscious animals is evolving as a critical tool for neuroscientists. The present study explored the effectiveness of an acclimation procedure in minimizing the stress experienced by the animal as assessed by alterations in physiological parameters including heart rate, respiratory rate, and serum corticosterone levels. Results confirm that as the stress of the protocol is minimized, there is a significant decrease in head movements and enhancement in data quality. The feasibility of improving the quality of fMRI data acquired in alert rats by utilizing a relatively simple technique is presented.
Significance Statement-Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.
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