Profiling nonhuman primate germline RNA to understand the legacy of early life stress.

Exposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well-being could be triggered by discrete environmental events or pervasive early life stress (ELS) resulting for example from adverse caregiving. Recent data mostly collected from rodents exposed to anthropogenic stressors suggest that one way via which the detrimental effects of such stress extend beyond the exposed population to future offspring is via stress-induced alterations of RNA found in the paternal germline. In contrast, less attention has been paid to how naturally occurring stress in males might influence offspring biology and behavior. In this study, we used a translational nonhuman primate model of ELS caused by naturally occurring adverse caregiving of infant macaques to (1) profile total RNA in the adolescent male germline, and (2) identify how those RNA profiles are affected by exposure to ELS. Our findings that the top 100 transcripts identified correspond to transcripts related to germline biology and reproduction demonstrate the validity and feasibility of profiling RNA in the germline of rhesus macaques. While our small sample sizes precluded definitive assessment of stress-induced alterations of RNA in the male germline of rhesus macaques that experienced ELS, our study sets the foundation for future investigations of how early adversity might alter the male germline, across species and in experimental protocols that involve anthropogenic vs natural stressors.

Effects of early life stress on cocaine intake in male and female rhesus macaques.

RATIONALE: It is critical to identify potential risk factors, such as a history of early life stress (ELS), that may confer specific vulnerabilities to increased drug intake. OBJECTIVE: In this study, we examined whether male and female rhesus monkeys with a history of ELS (infant maltreatment; MALT) demonstrated significantly greater cocaine intake compared with controls. METHODS: Monkeys were trained to self-administer cocaine during 4-h sessions at a peak dose (0.003-0.1 mg/kg/infusion; extended access, "EA peak") and a dose of 0.1 mg/kg/infusion (EA 0.1) of cocaine. These data were compared with data obtained previously in monkeys trained during 1-h limited access (LA) sessions at the same peak dose of cocaine used here (Wakeford et al. Psychopharmacology, 236:2785-2796, 2019). RESULTS: Monkeys significantly increased total number of infusions earned in EA compared with LA, but total session response rates significantly decreased in EA compared with LA. There was no evidence of escalation in drug intake when we compared response rates to obtain the first 20 cocaine infusions between LA and EA peak conditions. Moreover, there was no evidence of escalation in drug intake during an additional 7 weeks of self-administration at 0.1 mg/kg/injection. CONCLUSIONS: The current study expands on previous reports demonstrating that rhesus macaques did not escalate cocaine intake under the experimental conditions employed and extended these findings by using a unique population of nonhuman primates with a history of infant MALT to test the hypothesis that ELS is a risk factor for escalation of cocaine intake in nonhuman primates. There was no clear evidence of escalation in cocaine intake as a consequence of ELS.

Sex differences in rhesus monkey toy preferences parallel those of children.

Sex differences in toy preferences in children are marked, with boys expressing stronger and more rigid toy preferences than girls, whose preferences are more flexible. Socialization processes, parents, or peers encouraging play with gender-specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically-determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough-and-tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans.