Effects of Chronic and Acute Intranasal Oxytocin Treatments on Temporary Social Separation in Adult Titi Monkeys (Plecturocebus cupreus)

Abstract

In socially monogamous titi monkeys, involuntary separation from a pair mate can produce behavioral distress and increased cortisol production. The neuropeptide oxytocin (OXT) is thought to play an important role in the separation response of pair-bonded species. Previous studies from our lab have shown that chronic intranasal oxytocin (IN OXT) during development can have long-term effects on adult social behavior. In the current study, we examined the chronic and acute effects of IN OXT or Saline (SAL) on the subjects’ response to a brief separation from their pair mates. Subjects with a history of chronic IN OXT or SAL treatment during development received a single dose of OXT or SAL as adults 30 min before being separated from their pair mate. Chronic treatment consisted of a daily dose of IN OXT (0.8 IU/kg) or SAL (control) from 12 to 18 months of age. Subjects (N = 29) were introduced to a pair mate at 30 months of age. After the pairs had cohabitated for 5 months, pairs underwent two “Brief Separation” (OXT and SAL) and two “Non-Separation” (OXT and SAL) test sessions. Vocalizations and locomotion were measured as behavioral indices of agitation or distress during the Brief Separation and Non-Separation periods (30 min each). We collected blood samples after the Brief Separation and Non-Separation periods to measure cortisol levels. Our results showed subjects treated with chronic OXT had a reduction in long call and peep vocalizations compared to subjects treated with chronic SAL. Subjects treated with chronic SAL and acute OXT produced more peeps and long calls compared to animals treated with acute SAL; however, patterns in this response depended on sex. Cortisol and locomotion were significantly higher during the Brief Separation period compared to the Non-Separation period; however, we did not find any treatment or sex effects. We conclude that chronic IN OXT given during development blunts the separation response, while acute OXT in chronic SAL subjects had sexually dimorphic effects, which could reflect increased partner seeking behaviors in males and increased anxiety in females.

Intranasal oxytocin does not change partner preference in female titi monkeys (Plecturocebus cupreus), but intranasal vasopressin decreases it

“…One experimenter was holding the subject while another dripped the treatment with a pipette of 45 μL for each nostril, alternating nostrils. After each drip, the experimenter placed a finger over the nostril for a few seconds to prevent the subject from sneezing out the compound, until the compound was absorbed 36 …”

“…We gave the treatments dissolved in saline in two deliveries of 45 μL each per nostril (for a total of 180 μL). Doses of OT were based on previous work in prairie voles and juvenile titi monkeys, 22,36,39,40 and doses of AVP on a previous study in male titi monkeys. 5 The testing days for each animal were spaced at least 3 days apart to ensure complete elimination of the previous treatment.…”

“…After each drip, the experimenter placed a finger over the nostril for a few seconds to prevent the subject from sneezing out the compound, until the compound was absorbed. 36 After the administration of a treatment, an uptake period of 30 min 41 was observed during which the female subject and her partner were filmed in their home cage. After the 30 min of uptake, the subject and the stimulus males were released in the testing apparatus.…”

“…In addition, OT and AVP activity are influenced by steroid hormones, with OT being estrogen‐dependent, and some AVP neurons being androgen‐dependent 34,35 . These sex differences can help explain differences in the reactions of males and females to treatment with IN‐OT 22,36 . For example, female (but not male) titi monkeys which received chronic treatment with IN‐OT as periadolescents showed a blunted response to separation from their pair mate as adults 36 ; while adolescent IN‐OT facilitated adult partner preference in males but not in females 22 …”

“…34,35 These sex differences can help explain differences in the reactions of males and females to treatment with IN-OT. 22,36 For example, female (but not male) titi monkeys which received chronic treatment with IN-OT as periadolescents showed a blunted response to separation from their pair mate as adults 36 ; while adolescent IN-OT facilitated adult partner preference in males but not in females. 22 To address these sex differences, and to better understand the mechanistic basis of attachment in adult female primates, we performed a pharmacological study on the effects of OT and AVP on pair bond maintenance in female titi monkeys.…”