Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem

Abstract

Intranasal oxytocin affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of oxytocin and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue.

Challenges to the Pair Bond: Neural and Hormonal Effects of Separation and Reunion in a Monogamous Primate

“…The regional similarities but mechanistic differences are expected in the context of convergent evolution by which selection acts on similar structures and processes in ways unique within particular lineages. Studies in humans should take into account emerging information regarding the distribution of these receptors in humans (Freeman et al, 2016b). Future studies should also use neurochemically specific PET tracers, where available, to more closely identify the specific peptide and monoamine systems involved in various aspects of attachment.…”

Oxytocin pathways in the intergenerational transmission of maternal early life stress

“…The OTR expressing gene ( OXTR ) is located on chromosomal region 3p25–3p26.2, spans 17 kb, and consists of 3 introns and 4 exons (Gimpl and Fahrenholz, 2001). Studies on distribution patterns of OTRs in human post mortem brains found high OTR expression in amygadaloid nuclei, cingulate cortex, the hypothalamic medial preoptic area (MPOA), PVN, ventromedial nucleus, the solitary nucleus, and the spinal trigeminal nucleus (Boccia et al, 2013; Freeman et al, 2016). Given this wide spatial distribution of OTRs in the brain, OT is able to modulate an array of CNS-dependent processes such as social cognition, motivated behavior, and emotion regulation.…”

Localization of oxytocin receptors in the prairie vole (Microtus ochrogaster) neocortex

“…Furthermore, differences in the neuroanatomical distribution of OTR have been able to account for some of the differences in social organization across vole species (Insel and Shapiro 1992, Lim, et al 2004, Young and Wang 2004). The subcortical distribution of OTR has been examined in a wide variety of species, including but not limited to: rats, mice, several vole species, marmosets, coppery titi monkeys, rhesus macaques, and humans (Insel and Shapiro 1992, Freeman, et al 2016, Vaccari, et al 1998, Gould and Zingg 2003, Freeman, et al 2014, Freeman, et al 2014, Schorscher-Petcu, et al 2009). However, neocortical OTR distribution has gone largely unquantified, even though in many of these papers there are clearly visible areas of high OTR density within the neocortex.…”

“…These findings support the idea that the etiology of ASD may involve altered OTR distribution throughout the brain. Unfortunately, studies exploring the neuroanatomical distribution of OTR within the human brain have yet to characterize cortical regions (Freeman, et al 2016). Given our finding of dense OTR binding with the prairie vole neocortex, further studies are warranted to determine the prevalence of OTR within human neocortex, particularly motor and sensory association regions.…”

“…Then the 125 I-OVTA binding was quantified using ImageJ (NIH; Bethesda, MD, USA) to measure optical density. These techniques have been described previously (Freeman, et al 2016). Films were scanned and digitized using an Epson Perfection V500 Photo scanner.…”