The μ opioid receptor (MOR) and κ opioid receptor (KOR) have been implicated in pair-bond formation and maintenance in socially monogamous species. Utilizing monogamous titi monkeys (Callicebus cupreus), the present study examined the potential role opioids play in modulating the response to separation, a potent challenge to the pair-bond. In Experiment 1, paired male titi monkeys were separated from their pair-mate for 30-min and then received saline, naloxone (1.0mg/kg), morphine (0.25mg/kg), or the KOR agonist, U50,488 (0.01, 0.03, or 0.1mg/kg) in a counter-balanced fashion, immediately prior to a 30-min reunion with their mate. Blood samples were collected immediately prior to and after the reunion. Males receiving morphine approached females less, initiated contact less, and females broke contact with the males less. The increase in cortisol in response to naloxone was greater compared to vehicle, and the increase in cortisol in response to the high dose of U50,488 compared to vehicle approached significance. In Experiment 2, paired males were treated with the KOR antagonist, GNTI (0.1, 0.3, or 1.0mg/kg), or saline 24h prior to a 60-min separation from their mate. Blood samples were collected at the time of injection and immediately before and after separation. Administration of the low dose of GNTI decreased the locomotor component of the separation response compared to vehicle. The present study found that the opioid system is involved in both the affiliative and separation distress components of a pair-bond, and these components are regulated by different opioid receptors.

The opioid system is involved in infant-mother bonds and adult-adult bonds in many species. We have previously shown that μ opioid receptors (MORs) and κ opioid receptors (KORs) are involved in regulating the adult attachment of the monogamous titi monkey. The present study sought to determine the distribution of MOR and KOR in the titi monkey brain using receptor autoradiography. We used [(3)H][D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) to label MORs and [(3)H]U69,593 to label KORs. MOR binding was heterogeneous throughout the titi monkey brain. Specifically, MOR binding was observed in the cingulate gyrus (CG), striatum, septal regions, diagonal band, amygdala, hypothalamus, hippocampus, and thalamus. Binding was particularly dense in the septum, medial amygdala, paraventricular nucleus of the hypothalamus, mediodorsal thalamus with moderate binding in the nucleus accumbens. Consistent with other primate species, MOR were also observed in "neurochemically unique domains of the accumbens and putamen" (NUDAPs). In general KOR binding was more homogenous. KORs were primarily found in the CG, striatum, amygdala and hippocampus. Dense KOR binding was observed in the claustrum. Relative MOR and KOR binding in the titi monkey striatum was similar to other humans and primates, but was much lower compared to rodents. Relative MOR binding in the titi monkey hypothalamus was much greater than that found in rodents. This study was the first to examine MOR and KOR binding in a monogamous primate. The location of these receptors gives insight into where ligands may be acting to regulate social behavior and endocrine function.