Neuroanatomical distribution of oxytocin and vasopressin 1a receptors in the socially monogamous coppery titi monkey (Callicebus cupreus)

Abstract

The coppery titi monkey (Callicebus cupreus) is a socially monogamous New World primate that has been studied in the field and the laboratory to investigate the behavioral neuroendocrinology of primate pair bonding and parental care. Arginine vasopressin has been shown to influence male titi monkey pair-bonding behavior, and studies are currently underway to examine the effects of oxytocin on titi monkey behavior and physiology. Here, we use receptor autoradiography to identify the distribution of arginine vasopressin 1a receptor (AVPR1a) and oxytocin receptors (OXTR) in hemispheres of titi monkey brain (n=5). AVPR1a are diffuse and widespread throughout the brain, but the OXTR distribution is much more limited, with the densest binding being in the hippocampal formation (dentate gyrus, CA1 field) and the presubiculum (layers I and III). Moderate OXTR binding was detected in the nucleus basalis of Meynert, pulvinar, superior colliculus, layer 4C of primary visual cortex, periaqueductal gray (PAG), pontine gray, nucleus prepositus, and spinal trigeminal nucleus. OXTR mRNA overlapped with OXTR radioligand binding, confirming that the radioligand was detecting OXTR protein. AVPR1a binding is present throughout the cortex, especially in cingulate, insular, and occipital cortices, as well as in the caudate, putamen, nucleus accumbens, central amygdala, endopiriform nucleus, hippocampus (CA4 field), globus pallidus, lateral geniculate nucleus, infundibulum, habenula, PAG, substantia nigra, olivary nucleus, hypoglossal nucleus, and cerebellum. Furthermore, we show that, in the titi monkey brain, the OXTR antagonist ALS-II-69 is highly selective for OXTR and that the AVPR1a antagonist SR49059 is highly selective for AVPR1a. Based on these results and the fact that both ALS-II-69 and SR49059 are non-peptide, small-molecule antagonists that should be capable of crossing the blood-brain barrier, these two compounds emerge as excellent candidates for the pharmacological manipulation of OXTR and AVPR1a in future behavioral experiments in titi monkeys and other primate species.

Keywords: monogamy; neuroanatomy; neuropeptides; nonhuman primate; pair bonding; receptor binding.

Figure 1

Selectivity of radioligand binding in titi monkey brain tissue. Binding of the vasopressin 1a receptor (AVPR1a) radioligand ¹²⁵I-LVA (A, C, E) and the oxytocin receptor (OXTR) radioligand ¹²⁵I-OVTA (B, D, F) in adjacent titi monkey brain sections. Arrows highlight two representative regions with specific AVPR1a binding (lateral geniculate, LG) and OXTR binding (presubiculum, PSB). (A, B) Radioligand binding alone. (C, D) Radioligand binding in the presence of the AVPR1a antagonist SR49059. (E, F) Radioligand binding in the presence of the OXTR antagonist ALS-II-69. Note the diffuse ¹²⁵I-LVA binding throughout the brain, including the LG, which is reduced by SR49059 but not ALS-II-69. Likewise, ¹²⁵I-OVTA is reduced by ALS-II-69 but not by SR49059. These results suggest that both radioligands are highly selective for the respective titi monkey receptors.

Figure 2

Overall efficacy of the small molecule antagonists for displacing radioligand binding. Percent reduction in radioligand binding by SR49059 and ALS-II-69, averaged across three brain regions (LG, CeA, V1 for ¹²⁵I-LVA and DG, PSB, CA1 for ¹²⁵I-OVTA across animals for each radioligand. 10 nM SR49059 displaces off 74.0±1.7% (average±SEM) of binding of ¹²⁵I-LVA without significantly reducing binding of ¹²⁵I-OVTA (106.1±9.7%). 20 nM ALS-II-69 displaces off 43.0±5.5% of binding of ¹²⁵I-OVTA without significantly reducing binding of ¹²⁵I-LVA (101.5±7.1%).

Figure 3

Distribution of AVPR1a (A) and OXTR (B) in adjacent sections from one representative titi monkey brain, aligned with acetylcholinesterase (AChE) counterstain (C). Panel 1–3. Note the diffuse binding pattern of the AVPR1a radioligand throughout the cortex and striatum, while the OXTR binding pattern is much more restricted.

Figure 3

Distribution of AVPR1a (A) and OXTR (B) in adjacent sections from one representative titi monkey brain, aligned with acetylcholinesterase (AChE) counterstain (C). Panel 1–3. Note the diffuse binding pattern of the AVPR1a radioligand throughout the cortex and striatum, while the OXTR binding pattern is much more restricted.

Figure 3

Distribution of AVPR1a (A) and OXTR (B) in adjacent sections from one representative titi monkey brain, aligned with acetylcholinesterase (AChE) counterstain (C). Panel 1–3. Note the diffuse binding pattern of the AVPR1a radioligand throughout the cortex and striatum, while the OXTR binding pattern is much more restricted.

Figure 4

In situ hybridization results for OXTR mRNA compared to OXTR binding. A) Radioligand binding to OXTR. B) Binding of the antisense probe to OXTR mRNA. C) Binding of the sense probe, as a negative control to show areas of nonspecific probe binding.