Limits...
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.


Neural circuitry of high-density OT receptor binding sites. The 3D color model at the top depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations. Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group. Once fully registered and segmented, the statistical responses for each animal are averaged on a voxel-by-voxel bases. Those averaged voxels that are significantly different from baseline for positive BOLD are shown in their appropriate spatial location. Below are tables of these regions of interest for negative and positive BOLD at 10 and 20 min post ICV and IP OT. All areas are ranked in order of their significance. The brain areas highlighted in red and blue show significant changes in volumes of activation.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585275&req=5

Figure 2: Neural circuitry of high-density OT receptor binding sites. The 3D color model at the top depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations. Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group. Once fully registered and segmented, the statistical responses for each animal are averaged on a voxel-by-voxel bases. Those averaged voxels that are significantly different from baseline for positive BOLD are shown in their appropriate spatial location. Below are tables of these regions of interest for negative and positive BOLD at 10 and 20 min post ICV and IP OT. All areas are ranked in order of their significance. The brain areas highlighted in red and blue show significant changes in volumes of activation.

Mentions: The 3D color model at the top of Figure 2 depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988; Dumais et al., 2013). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations of vehicle and OT. Areas in red are the composite average of the significant increase in volumes of activation (number of voxels in a ROI) for positive BOLD from all rats for each condition. The median (Med) number of positive and negative voxels activated for both vehicle and OT within 10 min of ICV and IP (2.5 mg/kg) injection are shown in the tables below. These brain areas are ranked in order of their significance. These data from all brain areas are presented in the 3D activation maps. Of the 14 areas having a high density of OT binding sites, eight were significantly activated by ICV OT as shown in the table below highlighted in red. Only one area, the ventral subiculum, was activated by IP OT within the first 10 min of injection. There was no significant change in negative BOLD for ICV OT; while IP OT reduced activity in the anterior olfactory nucleus and ventral medial hypothalamus shown highlighted in blue. By 20 min post ICV OT injection, there were neither positive nor negative changes in BOLD signal that reached significance. At the same time period, IP OT caused a significant increase in BOLD signal in the accumbens shell and decrease in signal in the olfactory tubercles.


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)

Neural circuitry of high-density OT receptor binding sites. The 3D color model at the top depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations. Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group. Once fully registered and segmented, the statistical responses for each animal are averaged on a voxel-by-voxel bases. Those averaged voxels that are significantly different from baseline for positive BOLD are shown in their appropriate spatial location. Below are tables of these regions of interest for negative and positive BOLD at 10 and 20 min post ICV and IP OT. All areas are ranked in order of their significance. The brain areas highlighted in red and blue show significant changes in volumes of activation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585275&req=5

Figure 2: Neural circuitry of high-density OT receptor binding sites. The 3D color model at the top depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations. Areas in red are the localization of the activated voxels comprising the composite average from the rats in each experimental group. Once fully registered and segmented, the statistical responses for each animal are averaged on a voxel-by-voxel bases. Those averaged voxels that are significantly different from baseline for positive BOLD are shown in their appropriate spatial location. Below are tables of these regions of interest for negative and positive BOLD at 10 and 20 min post ICV and IP OT. All areas are ranked in order of their significance. The brain areas highlighted in red and blue show significant changes in volumes of activation.
Mentions: The 3D color model at the top of Figure 2 depicts the location of 14 brain areas in the rat reported to have a high density of OT receptor binding (De Kloet et al., 1985; van Leeuwen et al., 1985; Freund-Mercier et al., 1987; Tribollet et al., 1988; Dumais et al., 2013). These areas have been coalesced into a single volume (yellow) as shown in the lower 3D images for ICV and IP administrations of vehicle and OT. Areas in red are the composite average of the significant increase in volumes of activation (number of voxels in a ROI) for positive BOLD from all rats for each condition. The median (Med) number of positive and negative voxels activated for both vehicle and OT within 10 min of ICV and IP (2.5 mg/kg) injection are shown in the tables below. These brain areas are ranked in order of their significance. These data from all brain areas are presented in the 3D activation maps. Of the 14 areas having a high density of OT binding sites, eight were significantly activated by ICV OT as shown in the table below highlighted in red. Only one area, the ventral subiculum, was activated by IP OT within the first 10 min of injection. There was no significant change in negative BOLD for ICV OT; while IP OT reduced activity in the anterior olfactory nucleus and ventral medial hypothalamus shown highlighted in blue. By 20 min post ICV OT injection, there were neither positive nor negative changes in BOLD signal that reached significance. At the same time period, IP OT caused a significant increase in BOLD signal in the accumbens shell and decrease in signal in the olfactory tubercles.

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.