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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.


Onset of BOLD signal change: intracerebroventricular versus intraperitoneal oxytocin. Shown are the time-course plots for the change in BOLD signal in the superior colliculus following injection (arrow) of OT into the lateral cerebroventricle (gray, n = 8) or peritoneal cavity (black n = 11).
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Figure 3: Onset of BOLD signal change: intracerebroventricular versus intraperitoneal oxytocin. Shown are the time-course plots for the change in BOLD signal in the superior colliculus following injection (arrow) of OT into the lateral cerebroventricle (gray, n = 8) or peritoneal cavity (black n = 11).

Mentions: It should be noted that there is no clear dose-dependent change in the volume of activation for positive or negative BOLD at either time period for IP OT. A U-shaped pattern where OT doses of 0.1 and 2.5 are higher than the intermediate dose of 0.5 appears over most of the brain regions that show positive activation. Time-course plots showing the change in BOLD signal intensity in the superior colliculus for both ICV and IP administration of OT are presented in Figure 3. The superior colliculus was chosen because it showed robust activation with ICV (see Table S1 in Supplementary Material) and IP injections (see Table S3 in Supplementary Material). The change in BOLD signal occurs earlier with ICV injection by approximately 1 min as compared to IP (route × time: F11,187 = 37.64, P < 0.0001). The response peaks in around 2 min for ICV injection and about 4 min for IP injection.


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)

Onset of BOLD signal change: intracerebroventricular versus intraperitoneal oxytocin. Shown are the time-course plots for the change in BOLD signal in the superior colliculus following injection (arrow) of OT into the lateral cerebroventricle (gray, n = 8) or peritoneal cavity (black n = 11).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Onset of BOLD signal change: intracerebroventricular versus intraperitoneal oxytocin. Shown are the time-course plots for the change in BOLD signal in the superior colliculus following injection (arrow) of OT into the lateral cerebroventricle (gray, n = 8) or peritoneal cavity (black n = 11).
Mentions: It should be noted that there is no clear dose-dependent change in the volume of activation for positive or negative BOLD at either time period for IP OT. A U-shaped pattern where OT doses of 0.1 and 2.5 are higher than the intermediate dose of 0.5 appears over most of the brain regions that show positive activation. Time-course plots showing the change in BOLD signal intensity in the superior colliculus for both ICV and IP administration of OT are presented in Figure 3. The superior colliculus was chosen because it showed robust activation with ICV (see Table S1 in Supplementary Material) and IP injections (see Table S3 in Supplementary Material). The change in BOLD signal occurs earlier with ICV injection by approximately 1 min as compared to IP (route × time: F11,187 = 37.64, P < 0.0001). The response peaks in around 2 min for ICV injection and about 4 min for IP injection.

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.