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Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Ferris CF, Yee JR, Kenkel WM, Dumais KM, Moore K, Veenema AH, Kulkarni P, Perkybile AM, Carter CS - Front Behav Neurosci (2015)

Bottom Line: These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle.The change in BOLD signal to peripheral OT did not show any discernible dose-response.The results from this imaging study do not support a direct central action of peripheral OT on the brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational NeuroImaging, Northeastern University , Boston, MA , USA.

ABSTRACT
A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

No MeSH data available.


Hindbrain areas activated by intraperitoneal oxytocin. The 3D color model at the top left depicts the location of brain areas associated with activation of sensory afferents coming from the autonomic nervous system and synapses at the level of the brainstem and cerebellum. These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for IP vehicle (n = 12) and OT (n = 12). Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group following IP OT (2.5 mg). To the immediate right are 2D activation maps from the rat brain atlas showing the precise location of the significantly activated positive (red) voxels. The images to the far right show the localization of the voxels on the original neuroanatomical images.
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Figure 7: Hindbrain areas activated by intraperitoneal oxytocin. The 3D color model at the top left depicts the location of brain areas associated with activation of sensory afferents coming from the autonomic nervous system and synapses at the level of the brainstem and cerebellum. These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for IP vehicle (n = 12) and OT (n = 12). Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group following IP OT (2.5 mg). To the immediate right are 2D activation maps from the rat brain atlas showing the precise location of the significantly activated positive (red) voxels. The images to the far right show the localization of the voxels on the original neuroanatomical images.

Mentions: How does one account for the many brain areas, particularly those localized to the brainstem, that are activated by IP OT? One hypothesis focuses on the notion that IP OT can stimulate OT receptors found on many peripheral organs, e.g., heart, blood vessels, urogenital system, etc. (Gimpl and Fahrenholz, 2001) that are innervated by the autonomic nervous system. Hence, Figure 7 shows a composite of several brain areas involved in processing viscero-sensory information from the autonomic nervous system. Many of these areas (gigantocellularis, nucleus of solitary tract, and parabrachial, pedunculotegmentum) have direct connections with viscero-sensory neurons in the spinal cord (Cechetto et al., 1985; Menetrey and Basbaum, 1987; Bernard and Besson, 1990; Menetrey and De Pommery, 1991; Krutki et al., 1999). The nucleus of the solitary tract (NST), trigeminal, and vestibular areas receive sensory information from the cranial nerves (Torvik, 1956; Caous et al., 2012). Included in Figure 7 are areas of the cerebellum that also receive viscero-sensory innervation from spinal cord and cranial nerves (Newman and Paul, 1969; Rubia, 1970; Nisimaru and Katayama, 1995; Krutki et al., 1999). As in Figures 2 and 4, the images are color-coded and labeled for each 3D volumes and coalesced into a single volume (yellow) showing the location in red of the significant increase in volumes of activation for positive BOLD from all rats for each condition. These data are from the 2.5 mg dose of OT acquired in the first 10 min post injection (see Table S3 in Supplementary Material). The precise location of the positive voxels is shown in the columns to the right registered to the 2D axial section from the MRI rat atlas and the original anatomy. These composites are the average number of voxels showing a significant increase above baseline for vehicle (n = 12) and 2.5 mg/kg OT (n = 12).


Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

Ferris CF, Yee JR, Kenkel WM, Dumais KM, Moore K, Veenema AH, Kulkarni P, Perkybile AM, Carter CS - Front Behav Neurosci (2015)

Hindbrain areas activated by intraperitoneal oxytocin. The 3D color model at the top left depicts the location of brain areas associated with activation of sensory afferents coming from the autonomic nervous system and synapses at the level of the brainstem and cerebellum. These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for IP vehicle (n = 12) and OT (n = 12). Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group following IP OT (2.5 mg). To the immediate right are 2D activation maps from the rat brain atlas showing the precise location of the significantly activated positive (red) voxels. The images to the far right show the localization of the voxels on the original neuroanatomical images.
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Related In: Results  -  Collection

License
Show All Figures
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Figure 7: Hindbrain areas activated by intraperitoneal oxytocin. The 3D color model at the top left depicts the location of brain areas associated with activation of sensory afferents coming from the autonomic nervous system and synapses at the level of the brainstem and cerebellum. These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for IP vehicle (n = 12) and OT (n = 12). Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group following IP OT (2.5 mg). To the immediate right are 2D activation maps from the rat brain atlas showing the precise location of the significantly activated positive (red) voxels. The images to the far right show the localization of the voxels on the original neuroanatomical images.
Mentions: How does one account for the many brain areas, particularly those localized to the brainstem, that are activated by IP OT? One hypothesis focuses on the notion that IP OT can stimulate OT receptors found on many peripheral organs, e.g., heart, blood vessels, urogenital system, etc. (Gimpl and Fahrenholz, 2001) that are innervated by the autonomic nervous system. Hence, Figure 7 shows a composite of several brain areas involved in processing viscero-sensory information from the autonomic nervous system. Many of these areas (gigantocellularis, nucleus of solitary tract, and parabrachial, pedunculotegmentum) have direct connections with viscero-sensory neurons in the spinal cord (Cechetto et al., 1985; Menetrey and Basbaum, 1987; Bernard and Besson, 1990; Menetrey and De Pommery, 1991; Krutki et al., 1999). The nucleus of the solitary tract (NST), trigeminal, and vestibular areas receive sensory information from the cranial nerves (Torvik, 1956; Caous et al., 2012). Included in Figure 7 are areas of the cerebellum that also receive viscero-sensory innervation from spinal cord and cranial nerves (Newman and Paul, 1969; Rubia, 1970; Nisimaru and Katayama, 1995; Krutki et al., 1999). As in Figures 2 and 4, the images are color-coded and labeled for each 3D volumes and coalesced into a single volume (yellow) showing the location in red of the significant increase in volumes of activation for positive BOLD from all rats for each condition. These data are from the 2.5 mg dose of OT acquired in the first 10 min post injection (see Table S3 in Supplementary Material). The precise location of the positive voxels is shown in the columns to the right registered to the 2D axial section from the MRI rat atlas and the original anatomy. These composites are the average number of voxels showing a significant increase above baseline for vehicle (n = 12) and 2.5 mg/kg OT (n = 12).

Bottom Line: These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle.The change in BOLD signal to peripheral OT did not show any discernible dose-response.The results from this imaging study do not support a direct central action of peripheral OT on the brain.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational NeuroImaging, Northeastern University , Boston, MA , USA.

ABSTRACT
A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

No MeSH data available.