R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced Vocalizations and Observable Behavior in Nonhuman Primates

Abstract

Many psychiatric disorders include elements of dysfunctional social behavior. Understanding the pharmacological underpinnings of social behavior in a nonhuman primate species that demonstrates a repertoire of complex behavior (e.g., aggression or affiliative behavior) may provide insights into novel medication approaches aimed at restoring social deficits. Specifically, squirrel monkeys (Samiri boliviensis) emit a rich array of vocalizations that provide information on socio‐emotional and behavioral states. These vocalizations often co‐occur with readily observable behaviors that are easily quantifiable, permitting analyses of various aspects of social behavior. Previous studies have indicated that affiliative, or prosocial, vocalizations (pulsed calls and chucks) and behavior (huddling) may be modulated by serotonin 2A (5HT2A) receptors. To begin to understand how 5HT2A receptor activation influences social behavior, we examined the effects of R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI), a potent and moderately selective 5HT2A agonist, on affiliative vocalizations and observable behavior in nonhuman primates. Pair‐housed squirrel monkeys (2 males, 2 females) were transferred to an observation chamber outside of the colony and vocalizations and huddling were recorded during test sessions. Saline or DOI (0.01 or 0.06 mg/kg, IM) was administered prior to 30 min sessions. Results show that vocalizations, in particular pulsed calls, were increased following administration of 0.01 mg/kg DOI (438 ± 28) relative to saline (190.5 ± 21.5); a higher dose of 0.06 mg/kg DOI elicited a number of vocalizations that were not different from saline (201.5 ± 88.5). Frequency of huddling was unaffected by saline or DOI administration, however, increases in general activity were observed following DOI administration at both doses in comparison to saline. A preliminary examination of potential sex differences suggests that there were no differences between males and females in huddling or total number of vocalizations, though males produced more alarm calls at the highest dose of DOI tested. These data suggest that 5HT2A receptor activation is sufficient for increasing affiliative vocalizations, but may not change other indices of prosocial behavior, such as huddling. Future studies will expand the list of behaviors captured to include positional analyses of each subject, as well as evaluating the contribution of other 5HT receptors to specific dimensions of prosocial behavior.Support or Funding InformationResearch support provided by R01DA048150 (SJK).