The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta)

“The neuroanatomical localization of OXTR using receptor autoradiography has been useful for identifying neural mechanisms of OT action in rodents (Ferguson et al., 2001; Young and Wang, 2004).”

“The neuroanatomical localization of OXTR using receptor autoradiography has been useful for identifying neural mechanisms of OT action in rodents (Ferguson et al., 2001; Young and Wang, 2004).”

“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”

“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”

“…vector gene manipulations, and transgenic mouse technology have led to the elucidation of the neural mechanisms underlying the effects of these neuropeptides and their receptors on these complex social behaviors (Dölen et al., 2013; Ferguson et al., 2001; Lim et al., 2004b; Owen et al., 2013).”

“However using IHC to stain for OXTR has been notoriously problematic; a study that tested six different OXTR antibodies found that all of them produced identical patterns of staining in brain tissue from wildtype and OXTR knockout mice, indicating their unreliability in detecting OXTR in rodent brain (Yoshida et al.,…”

“, 2004) and is related to the ability to localize sound in space (Fritz et al., 2007), which further supports the importance of the TB in this purportedly OT-sensitive ability.”

“In fact, it has been suggested that the cocktail party effect requires binaural processing of sound (Hawley et al., 2004) and is related to the ability to localize sound in space (Fritz et al., 2007), which further supports the importance of the TB in this purportedly OT-sensitive ability.”

“The SuG receives input from the retina, is organized to contain a map of visual space (Goldberg and Wurtz, 1972), and is thought to provide synaptic input to the deeper layers of the SC in order to mediate orienting movements in response to specific visual cues (Ma et al.”

“Indirect support for this idea comes from an IN-OT study in humans that reported increased functional coupling between the SC and the amygdala during a face viewing task (Gamer et al., 2010).”

“In rats, OXTR in the VMH regulate female sexual receptivity in an estrogen (E2) dependent manner (Bale et al., 2001; McCarthy et al., 1994).”

“Although the behavioral effects of OTare widely assumed to mediated by central OXTR, OT does cross react with the AVP receptors and vice versa (Manning et al., 2012), and some of the behavioral effects of OT are mediated by AVPR1A (Schorscher-Petcu et al.”

“Intranasally administered OT (IN-OT) modulates several aspects of social cognition and behavior, including increasing trust, eye-gaze, emotion recognition, empathy and socially reinforced learning (Guastella et al., 2012), and behaviors relevant to pair bonding (Scheele et al., 2013, 2012).”

“Thus, while OXTR in VMH in rhesus macaques resembles the majority of mammalian species, there are some differences across primates.”

“As rhesus macaques are amenable to intracranial manipulations (Gothard et al., 2007), including site-specific pharmacology, microdialysis, and electrophysiology, this species provides an excellent opportunity to explore the precise neural mechanisms by which OT modulates social cognition in primates.”

“There is evidence that roles of these peptides are conserved to some degree in humans (Scheele et al., 2013; Skuse et al., 2013), despite differences in the nature of social stimuli between rodent and man.”

“Intranasally administered OT (IN-OT) modulates several aspects of social cognition and behavior, including increasing trust, eye-gaze, emotion recognition, empathy and socially reinforced learning (Guastella et al., 2012), and behaviors relevant to pair bonding (Scheele et al., 2013, 2012).”

“…ligands that were developed specifically for use in human tissue for their ability to displace radioligand binding to hOXTR and hAVPR1A: a novel OXTR antagonist developed in our lab (ALS-II-69; Smith et al., 2013) and an AVPR1A antagonist developed by Sanofi Recherche (SR49059; Gal et al., 1993).”

“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al., 2010; Domes et al., 2013; Hollander et al., 2007).”

“More recently, IN-OT administration in rhesus macaques has been shown to increase central OT concentrations (Chang et al., 2012) (Modi et al., 2014) and to affect a variety of social behaviors including increasing gaze to the eye region of monkey faces (Ebitz et al., 2013), increasing both selfish…”

“The characteristics of the connectivity between the TB and other regions in the auditory pathway are considered to underlie the ability to localize sound sources in space (Schneggenburger and Forsythe, 2006).”

“A similar diversity in OXTR expression in found in rodents, as voles, mice, and rats each have unique distributions of OXTR binding (Burbach et al., 2006; Olazábal and Young, 2006).”

“Behavioral studies in NHPs suggest that OT modulates social behaviors related to affiliation, sexual behavior, and pair bonding (Smith et al., 2010; Snowdon et al., 2010).”

“The OT system is a potential target for enhancing social cognition in psychiatric disorders (Modi and Young, 2012), and several studies have now shown that IN-OT improves some aspects of social functioning in autism spectrum disorder (Andari et al.”

“Genetic studies also suggest that the OT receptor (OXTR) plays some role in face and emotion recognition and pair bonding behaviors in humans (Skuse et al., 2013; Walum et al., 2012).”

“Genetic studies also suggest that the OT receptor (OXTR) plays some role in face and emotion recognition and pair bonding behaviors in humans (Skuse et al., 2013; Walum et al., 2012).”

“This cholinergic input from NBM plays a critical role in selective attention, attentional effort, and motivation, specifically with respect to visual attention (Muir et al., 1993).”

“In humans, IN-OT affects the reaction to infant cries (Bakermans-Kranenburg et al., 2012) and infant laughter (Riem et al., 2012) and may even play a role in navigating the ‘‘cocktail party effect’’ (Tops et al., 2011), which is the phenomenon whereby an individual can focus one’s auditory…”

“We also detected modest OXTR mRNA in the PPT, which is another highly interconnected region of the brain that has been implicated in a variety of functions, including sleep, locomotion, reaction time, reinforcement learning, sensation, attention, and consciousness (Winn, 2006).”

“, 2012), and some of the behavioral effects of OT are mediated by AVPR1A (Schorscher-Petcu et al., 2010; Song et al., 2013).”

“Insights into the neural mechanisms of OT action in humans have been gained using brain imaging (Zink and Meyer-Lindenberg, 2012), but inferences on precise mechanisms of action based on these techniques are limited compared to studies using animal models.”

“…vector gene manipulations, and transgenic mouse technology have led to the elucidation of the neural mechanisms underlying the effects of these neuropeptides and their receptors on these complex social behaviors (Dölen et al., 2013; Ferguson et al., 2001; Lim et al., 2004b; Owen et al., 2013).”

“OXTR binding has been found in VMH in mice, rats, guinea pigs, prairie and montane voles, two species of Central America singing mice, and two species of the South American rodent the tuco-tuco (Beery et al., 2008).”

“In rats, OXTR in the VMH regulate female sexual receptivity in an estrogen (E2) dependent manner (Bale et al., 2001; McCarthy et al., 1994).”

“Our results with (125)I-LVA fully match the previously reported distribution of AVPR1A binding in the rhesus macaque (Young et al., 1999).”

“Behavioral studies in NHPs suggest that OT modulates social behaviors related to affiliation, sexual behavior, and pair bonding (Smith et al., 2010; Snowdon et al., 2010).”

“, 2012), and changing social visual attentional bias (Ebitz et al., 2013; Parr et al., 2013).”

“More recently, IN-OT administration in rhesus macaques has been shown to increase central OT concentrations (Chang et al., 2012) (Modi et al., 2014) and to affect a variety of social behaviors including increasing gaze to the eye region of monkey faces (Ebitz et al., 2013), increasing both selfish…”

“There is also evidence that OXTR in the VMH also play a role in the motivational switching between sexual behavior and feeding in rodents (Leng et al., 2008) and thus may have a role in regulating food intake and appetite in primates as well.”

“There were only two areas of consistent OXTR binding across all four primate species: NBM and SC (Loup et al., 1991; Schorscher-Petcu et al., 2009; S.M. Freeman et al., unpublished observations).”

“It should be noted that the small molecule competitors did not eliminate the areas of high density specific binding at the concentrations used, which is likely due to the fact that the small, nonpeptide competitors can act as allosteric modulators to affect the affinity of the orthosteric ligand (in our case, the pept…”

“The cholinergic subdivision, where we see OXTR expression, is the major source of cholinergic input to the midbrain and one of the major ascending arousal pathways in the brainstem (Kobayashi et al., 2002).”

“Furthermore, previous studies have reported that the density of OXTR expression does not correlate with electrophysiological responses to OT, as brain regions with low OXTR binding often display greater responses to OT than those with dense binding (Terenzi and Ingram, 2005; Wilson et al., 2005).”

“There has been growing interest in the role of OT in human social cognition (Young and Flanagan-Cato, 2012).”

“In primates, female rhesus macaque sexual behavior is highest during the peak in E2 during estrous and increases after estrogen treatment in ovariectomized rhesus macaques (Zehr et al., 1998).”

“6), and cholinergic input from the PPT strongly innervates the macaque superior colliculus (SC) (Ma et al., 1991).”

“…cries (Bakermans-Kranenburg et al., 2012) and infant laughter (Riem et al., 2012) and may even play a role in navigating the ‘‘cocktail party effect’’ (Tops et al., 2011), which is the phenomenon whereby an individual can focus one’s auditory attention on one particular stimulus and ‘‘tune out’’…”

“Sections were allowed to thaw as described above, then hybridized with the probes and washed as described previously with minor modifications (Inoue et al., 2013).”

“2), which is consistent with what was previously reported for these radioligands in this species (Toloczko et al., 1997; Young et al., 1999).”

“…ligands that were developed specifically for use in human tissue for their ability to displace radioligand binding to hOXTR and hAVPR1A: a novel OXTR antagonist developed in our lab (ALS-II-69; Smith et al., 2013) and an AVPR1A antagonist developed by Sanofi Recherche (SR49059; Gal et al., 1993).”

“Neurons in the PPT have also been shown to be active in monkeys during saccade tasks (Okada and Kobayashi, 2009) and to directly stimulate SC neurons and facilitate the initiation of saccadic eye movements (Kobayashi et al., 2001).”

“For the AVPR1A competitor SR49059, whose use to selectively occupy AVPR1A in a competitive binding approach has been suggested previously (Ala et al., 1997), we determined that the best concentration for SR49059 to bind to displace 125I-OVTA from hAVPR1A without affecting binding to hOXTR is 10 nM…”

“Two publications have used immunohistochemistry (IHC) with an OXTR antibody to identify areas of OXTR expression in the macaque brain (Boccia et al., 2001) and in human brain tissue (Boccia et al., 2013).”

“Oxytocin (OT) and vasopressin (AVP) are structurally related peptides that modulate a range of complex social behaviors, including maternal behavior, aggression, territoriality, social recognition, and social bonding (Freeman and Young, 2013).”

“(Salvatore et al., 1998; Young et al., 1999).”

“Furthermore, previous studies have reported that the density of OXTR expression does not correlate with electrophysiological responses to OT, as brain regions with low OXTR binding often display greater responses to OT than those with dense binding (Terenzi and Ingram, 2005; Wilson et al., 2005).”

“Oxytocin may be an important modulator of nucleus basalis, as indicated by recent autoradiography and in situ hybridization data from macaques (Freeman et al. 2014).”

“…and early cortical visual areas and cholinergic nuclei controlling sensory processing in these modalities, suggesting the involvement of OXT in a variety of functions relevant to social cognition, including modulating visual attention, processing, and sensory stimuli (Freeman et al., 2014a, 2014b).”