Functional magnetic resonance imaging and the neurobiology of vasopressin and oxytocin
Introduction
Vasopressin (AVP) and oxytocin (OXT) comprise a phylogenetically old super family of chemical signals in both vertebrates and invertebrates. The conservation and dispersion of AVP and OXT signalling systems across the animal kingdom attests to their functional significance in evolution. In addition to their function in physiological homoeostasis, these neuropeptides evolved a role in social behaviours related to aggression and affiliation. AVP has a demonstrated role in aggression enhancing agonistic behaviour in amphibians, fish, birds and mammals, including humans. In contrast, OXT is a key hormone enabling milk let-down during breastfeeding and the enhancement of affiliative behaviours associated with caring for young. While both neuropeptides function as neurohormones released from the posterior pituitary gland into the general circulation, their effects on behaviour are achieved by direct neurochemical signalling in the central nervous system. Precisely how and where these neuropeptides act to affect such important behaviours as aggression and affiliation are not entirely clear. With the advent of new non-invasive imaging techniques like functional magnetic resonance imaging (fMRI) it is possible to gain new insights into the neurobiology of these neuropeptides. To this end, fMRI with 3D computational analysis in conscious rats was used to study the role AVP in aggressive motivation and the role of OXT in pup suckling and maternal behaviour.
Functional MRI with ultra-high field animal scanners (≥4.7 T) provide exceptional temporal and spatial resolution making it possible to map in seconds functionally relevant neural networks activated by a variety of environmental and chemical stimuli (Ferris et al., 2001; Tenney et al., 2004; Brevard et al., 2006a, Brevard et al., 2006b). Increased neuronal activity is accompanied by an increase in metabolism concomitant with changes in cerebral blood flow and blood volume to the area of elevated neural activity. Blood oxygen level-dependent (BOLD) fMRI is a technique sensitive to the oxygenation status of haemoglobin (Ogawa et al., 1990). While fMRI has neither the cellular spatial resolution of immunostaining, nor the millisecond temporal resolution of electrophysiology, it does show synchronized changes in neuronal activity across multiple brain areas, providing a unique insight into functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behavioural states. This chapter presents a discussion on the technology and methods for performing imaging studies on awake male rats responding to aggression-provoking stimuli and awake lactating dams responding to pup suckling. These unique experimental models enable two questions: (1) What is the role of centrally released AVP in aggressive motivation? (2) What role does OXT play in suckling-induced brain activation?
Section snippets
Imaging conscious animals
Animals are acquired and cared for in accordance with the guidelines published in the Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publications No. 85-23, Revised 1985) and adhere to the National Institutes of Health and the American Association for Laboratory Animal Science guidelines. The protocols used in these studies were in compliance with the regulations of the Institutional Animal Care and Use Committee at the University Massachusetts Medical School.
Imaging aggressive motivation and the role of vasopressin neurotransmission
There is a general consensus that AVP functions to facilitate aggressive behaviour across multiple species (Ferris, 2005). Microinjections of AVP into the hypothalamus or amygdala and cerebrointraventricular administration in rodents leads to enhanced aggression while administration of a selective linear V1a antagonist, Manning compound [1-β-mercapto-β,β-cyclopentamethylene propionic acid 2-[0-(methyl) tyrosine] arginine vasopressin, blocks aggressive behaviour (Ferris and Potegal, 1988;
Imaging the “nursing” brain and the role of oxytocin neurotransmission
OXT synthesis mainly occurs in neurons of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. It is transported to and released from nerve terminals in the posterior pituitary and various regions of the brain. Suckling stimulates the release of OXT simultaneously into the bloodstream and central nervous system of postpartum rats (Neumann et al., 1993a). Systemically, this neurohormone enhances smooth muscle contractility, which is important for milk ‘let-down’ during
Final summary
These data from two unique experimental paradigms using fMRI, support and extend our previous understanding of AVP's and OXT's effect on brain activity under complex social and emotional conditions. Blocking V1a receptors suppresses aggressive motivation in bench-top studies and during imaging. The imaging data are characterized by a general reduction in BOLD signal particularly in areas identified as the putative neural circuit of aggressive motivation. However, this response is not due to a
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Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain
2015, PsychoneuroendocrinologyCitation Excerpt :Administration of oxytocin into the cerebral ventricles elicits maternal behavior in virgin rats (Pedersen et al., 1982) and activates brain areas involved in maternal behavior (Ferris, 2008). On the contrary, blocking of oxytocin actions inhibits these same areas (Ferris, 2008) and markedly disrupts maternal behavior (Pedersen and Boccia, 2003; Sabihi et al., 2014), and maternal memory (D’Cunha et al., 2011). OTRs, which mediate the actions of oxytocin, are increased during the post partum period (Insel, 1990).
Long-term programming of enhanced aggression by peripuberty stress in female rats
2013, PsychoneuroendocrinologyCitation Excerpt :In male rats, distinct correlations were found between vasopressin release in the lateral septum and bed nucleus of the stria terminalis and aggressive behavior displays (Veenema et al., 2010). Furthermore, AVP treatment increases brain activity in aggression-related areas (Ferris, 2008), and conversely, antagonists of AVP receptors 1A were found to reduce aggression while simultaneously suppressing the pattern of brain activation caused by an intruder (Ferris, 2008). Given the above mentioned literature and our own findings showing an increase of AVP and aggressive behavior in stressed females, our results showing opposite intragroup correlations between AVP and maternal aggression (positive in control and negative in stress group) suggests a different role of AVP on maternal aggression depending on life experiences.
Intranasal administration of oxytocin: Behavioral and clinical effects, a review
2013, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Taking together the events described in the preceding part of our review, we recognize a specific cascade of events potentially occurring after IN-administration of OT. All available evidence suggests that vasopressin works along similar mechanisms but to different effects via other brain areas (Ferris, 2008; Levasseur et al., 2004). Similar cascades of neural activation mechanisms may occur after IN-administration of other neuropeptides or neuroactive substances as well, but generally we have no clear idea yet about their features and neuronal distribution.
Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis
2013, Schizophrenia ResearchCitation Excerpt :Changes in stress-related hormones such as AVP may be associated with the clinical symptoms and cognition observed in schizophrenia. Whereas OT influences stress management, cardiovascular regulation, and under some conditions may have amnestic effects on verbal learning and memory; AVP is more typically associated with vigilance, mobilization, increased reactivity to stressors, and improvements in verbal learning and memory (Strupp et al., 1983; Fehm-Wolfsdorf and Born, 1991; Carter, 1998; Carter et al., 2008; Ferris, 2008; Heinrichs et al., 2009; Gutkowska and Jankowski, 2012). Disruptions and interactions among these hormones may regulate physiology, behavior, and cognition allowing shifts between positive social behaviors and defensive states that are associated with the clinical symptoms of schizophrenia.