Behavior In Nonhuman Primates Research Articles

Maternal Western-style diet reduces social engagement and increases idiosyncratic behavior in Japanese macaque offspring

Recent evidence in humans and animals indicates an association between maternal obesity and offspring behavioral outcomes. In humans, increased maternal body mass index has been linked to an increased risk of children receiving a diagnosis of early-emerging neurodevelopmental disorders such as Attention Deficit/Hyperactivity Disorder (ADHD) and/or Autism Spectrum Disorder (ASD). However, a limited number of preclinical studies have examined associations between maternal Western-Style Diet (mWSD) exposure and offspring social behavior. To our knowledge, this is the first study to investigate relationships between mWSD exposure and social behavior in non-human primates. Since aberrant social behavior is a diagnostic criterion for several neurodevelopmental disorders, the current study focuses on examining the influence of maternal nutrition and metabolic state on offspring social behavior in Japanese macaques (Macaca fuscata). We found that mWSD offspring initiated less affiliative social behaviors as well as proximity to a peer. Using path analysis, we found that the association between mWSD consumption and reduced offspring social engagement was statistically mediated by increased maternal interleukin (IL)-12 during the third trimester of pregnancy. Additionally, mWSD offspring displayed increased idiosyncratic behavior, which was related to alterations in maternal adiposity and leptin in the third trimester. Together, these results suggest that NHP offspring exposed to mWSD exhibit behavioral phenotypes similar to what is described in some early-emerging neurodevelopmental disorders. These results provide evidence that mWSD exposure during gestation may be linked to increased risk of neurodevelopmental disorders and provides targets for prevention and intervention efforts.

Active vision during prey capture in wild marmoset monkeys

A foundational pressure in the evolution of all animals is the ability to travel through the world, inherently coupling the sensory and motor systems. While this relationship has been explored in several species,1-4 it has been largely overlooked in primates, which have typically relied on paradigms in which head-restrained subjects view stimuli on screens.5 Natural visual behaviors, by contrast, are typified by locomotion through the environment guided by active sensing as animals explore and interact with the world,4,6 a relationship well illustrated by prey capture.7-12 Here, we characterized prey capture in wild marmoset monkeys as they negotiated their dynamic, arboreal habitat to illustrate the inherent role of vision as an active process in natural nonhuman primate behavior. Not only do marmosets share the core properties of vision that typify the primate Order,13-18 but they are prolific hunters that prey on a diverse set of prey animals.19-22 Marmosets pursued prey using vision in several different contexts, but executed precise visually guided motor control that predominantly involved grasping with hands for successful capture of prey. Applying markerless tracking for the first time in wild primates yielded novel findings that precisely quantified how marmosets track insects prior to initiating an attack and the rapid visually guided corrections of the hands during capture. These findings offer the first detailed insight into the active nature of vision to guide multiple facets of a natural goal-directed behavior in wild primates and can inform future laboratory studies of natural primate visual behaviors and the supporting neural processes.

Performance-gated deliberation: A context-adapted strategy in which urgency is opportunity cost.

Finding the right amount of deliberation, between insufficient and excessive, is a hard decision making problem that depends on the value we place on our time. Average-reward, putatively encoded by tonic dopamine, serves in existing reinforcement learning theory as the opportunity cost of time, including deliberation time. Importantly, this cost can itself vary with the environmental context and is not trivial to estimate. Here, we propose how the opportunity cost of deliberation can be estimated adaptively on multiple timescales to account for non-stationary contextual factors. We use it in a simple decision-making heuristic based on average-reward reinforcement learning (AR-RL) that we call Performance-Gated Deliberation (PGD). We propose PGD as a strategy used by animals wherein deliberation cost is implemented directly as urgency, a previously characterized neural signal effectively controlling the speed of the decision-making process. We show PGD outperforms AR-RL solutions in explaining behaviour and urgency of non-human primates in a context-varying random walk prediction task and is consistent with relative performance and urgency in a context-varying random dot motion task. We make readily testable predictions for both neural activity and behaviour.

The G-protein biased kappa opioid agonists, triazole 1.1 and nalfurafine, produce non-uniform behavioral effects in male rhesus monkeys

Kappa-opioid receptor (KOR) agonists have been studied as potential treatments for pain, pruritus, and substance-use disorders, but prototypical KOR agonists produce side-effects like dysphoria and sedation. Atypical KOR agonists that exhibit G-protein biased signaling at the KOR have been reported to produce therapeutic-like effects with fewer or reduced side effects relative to prototypical KOR agonists. In the current report, behavioral profiles were determined using a behavioral scoring system that was modified to quantify drug-induced behaviors in nonhuman primates (NHPs). Profiles were determined for a prototypical and two biased KOR agonists, alone and combined with the mu-opioid receptor (MOR) agonist, oxycodone. Five adult male rhesus monkeys implanted with intravenous catheters were administered a range of doses of the KOR agonist, U50-488H (0.01–0.1 mg/kg) and the biased KOR agonists, nalfurafine (0.0001–0.001 mg/kg) and triazole 1.1 (0.32–1.0 mg/kg), alone and combined with the MOR agonist, oxycodone (0.01–0.32 mg/kg). In addition, the largest triazole 1.1 dose tested (1.0 mg/kg) was administered in time-course determinations (0–56 min), alone and combined with oxycodone (0.1 mg/kg). U50-488H and nalfurafine produced sedative-like and motor-impairing effects. Triazole 1.1 had a milder side-effect profile, in some instances producing sedative-like effects but to a lesser degree compared with the other KOR agonists, particularly for lip droop and rest/sleep posture. All KOR agonists reduced oxycodone-induced scratch, but nalfurafine produced behavior-disrupting and sedative-like effects when combined with oxycodone that were not observed with triazole 1.1. The duration of triazole 1.1's behavioral effects was relatively short, dissipating entirely by 56 min. Our results suggest that KOR agonists with comparable pharmacology to triazole 1.1 may be useful therapeutics with reduced side-effect profiles, and the mechanisms conferring these benefits may be attributed to factors other than G-protein bias.

Two‐monkey fMRI setup for investigating multifaceted aspects of social cognition and behavior involving a real‐live conspecific

While brain research over the past decades has shed light on the neural correlates of social cognition and behavior in human and non-human primates, most of this research has been performed in virtual settings requiring subjects to observe pictures or recorded videos instead of observing or interacting with another real-live individual. Here we present a two-monkey fMRI setup, allowing examining whole brain responses in macaque monkeys while they observe or interact face-to-face with another real-live conspecific. We tested this setup by comparing overall brain responses during observation of conspecific hand actions in a virtual (observation of recorded videos of actions) or live context (observation of a real-live conspecific performing actions). This dyadic monkey fMRI setup allows examining brain-wide responses in macaque monkeys during different aspects of social behavior, including observation of real-live actions and sensations, social facilitation, joint-attention and social interactions.

Nonhuman primate abnormal behavior: Etiology, assessment, and treatment.

Across captive settings, nonhuman primates may develop an array of abnormal behaviors including stereotypic and self-injurious behavior. Abnormal behavior can indicate a state of poor welfare, since it is often associated with a suboptimal environment. However, this may not always be the case as some behaviors can develop independently of any psychological distress, be triggered in environments known to promote welfare, and be part of an animal's coping mechanism. Furthermore, not all animals develop abnormal behavior, which has led researchers to assess risk factors that differentiate individuals in the display of these behaviors. Intrinsic risk factors that have been identified include the animal's species and genetics, age, sex, temperament, and clinical condition, while environmental risk factors include variables such as the animal's rearing, housing condition, husbandry procedures, and research experiences. To identify specific triggers and at-risk animals, the expression of abnormal behavior in captive nonhuman primates should be routinely addressed in a consistent manner by appropriately trained staff. Which behaviors to assess, what assessment methods to use, which primates to monitor, and the aims of data collection should all be identified before proceeding to an intervention and/or treatment. This article provides guidance for this process, by presenting an overview of known triggers and risk factors that should be considered, steps to design a comprehensive evaluation plan, and strategies that might be used for prevention or treatment. It also outlines the tools and processes for assessing and evaluating behavior in an appendix. This process will lead to a better understanding of abnormal behavior in captive primate colonies and ultimately to improved welfare.

Early Effects of Cranial Irradiation by High Energy Protons on Visuomotor behavior in Nonhuman Primates

Early Effects of Cranial Irradiation by High Energy Protons on Visuomotor behavior in Nonhuman Primates

Cost-Benefit Trade-Offs of Aquatic Resource Exploitation in the Context of Hominin Evolution

While the exploitation of aquatic fauna and flora has been documented in several primate species to date, the evolutionary contexts and mechanisms behind the emergence of this behavior in both human and non-human primates remain largely overlooked. Yet, this issue is particularly important for our understanding of human evolution, as hominins represent not only the primate group with the highest degree of adaptedness to aquatic environments, but also the only group in which true coastal and maritime adaptations have evolved. As such, in the present study we review the available literature on primate foraging strategies related to the exploitation of aquatic resources and their putative associated cognitive operations. We propose that aquatic resource consumption in extant primates can be interpreted as a highly site-specific behavioral expression of a generic adaptive foraging decision-making process, emerging in sites at which the local cost-benefit trade-offs contextually favor aquatic over terrestrial foods. Within this framework, we discuss the potential impacts that the unique intensification of this behavior in hominins may have had on the evolution of the human brain and spatial ecology.

Fibroblast Growth Factor 21 Facilitates the Homeostatic Control of Feeding Behavior.

Fibroblast growth factor 21 (FGF21) is a stress hormone that is released from the liver in response to nutritional and metabolic challenges. In addition to its well-described effects on systemic metabolism, a growing body of literature now supports the notion that FGF21 also acts via the central nervous system to control feeding behavior. Here we review the current understanding of FGF21 as a hormone regulating feeding behavior in rodents, non-human primates, and humans. First, we examine the nutritional contexts that induce FGF21 secretion. Initial reports describing FGF21 as a ‘starvation hormone’ have now been further refined. FGF21 is now better understood as an endocrine mediator of the intracellular stress response to various nutritional manipulations, including excess sugars and alcohol, caloric deficits, a ketogenic diet, and amino acid restriction. We discuss FGF21’s effects on energy intake and macronutrient choice, together with our current understanding of the underlying neural mechanisms. We argue that the behavioral effects of FGF21 function primarily to maintain systemic macronutrient homeostasis, and in particular to maintain an adequate supply of protein and amino acids for use by the cells.

Increasing Central Serotonin with 5-hydroxytryptophan Disrupts the Inhibition of Social Gaze in Nonhuman Primates.

To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted amongst patient populations treated with serotonergic drugs. However, those in the field lack a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques (both sexes) to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orienting and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in nonhuman primates and offer translational insights for the role of the serotonergic system in social gaze.SIGNIFICANCE STATEMENT Behavioral changes arising from pharmacological agents that target serotonergic functions are complex and difficult to predict. Here, we examined the causal impacts of administering the direct precursor of serotonin, 5-HTP, on orienting and inhibiting social gaze in nonhuman primates. 5-HTP increased central concentrations of serotonin and selectively impaired the ability of monkeys to inhibit orienting to faces while similarly impairing the ability of monkeys to orient to face and control images. These behavioral gaze impairments were systematically associated with a downregulation of arousal and motivational states, indexed by pupil constriction, increased time to initiate trials, and increased reaction time. These findings provide a causal link between 5-HTP and social gaze behaviors in nonhuman primates and provide translational insights about serotonergic interventions.

Minimal age-related variation in bipedal behavior in Sapajus

Our understanding of how bipedalism evolved in hominins has been refined through studies of bipedal behavior in non-human primates, both in the wild and in the laboratory. Bipedal behavior in non-human primates makes up a relatively small portion of their behavioral repertoire. Understanding when bipedal behaviors occur and how bipedal behaviors emerge can provide further insight into the context in which bipedal behaviors may have evolved. Here, we examine age-related variation in bipedal behavior in wild bearded capuchins (Sapajus libidinosus). 2,209 records of bipedal posture and locomotion, activity state, and substrate used during bipedal behavior (17.2% of all records of positional behavior) were examined for individuals ranging from 3 months to 15 years or older in two groups (32 individuals in total). Apart from very young individuals that were carried by older conspecifics, individuals of all ages showed similar rates and patterns of bipedal behaviors. Bipedal postures were used predominantly during feeding and foraging, most often in arboreal settings, and most often with their prehensile tail grasping, or in contact with, the substrate. Bipedal locomotion occurred most often on terrestrial substrates and comprised only 3% of all records of bipedal behavior.

A baboon walking on a treadmill: the use of positive reinforcement techniques to study bipedal walking in non-human primates

To date, the use of positive reinforcement techniques to study locomotion in non-human primates remains poorly developed. However, using cooperative animals that can freely move in experimental setup allows us to collect valuable and relevant data and makes these repeatable and comparable between species. Based on the current knowledge and our experience, we present an experimental approach that aims at reaching the standards of the study of human movement in a non-human primate, the olive baboon, Papio anubis, thanks to the use of positive reinforcement techniques. This report documents the training protocol that we set up at the Primatology station of the CNRS (France). We further elaborate on the importance of conducting such experiments for a better and finer understanding of the bipedal behaviour in non-human primates. Experimental studies including cooperative animals that can freely move are likely to represent valuable experimental tools to fill important gaps of knowledge in the study of locomotion in general, and in the study of the acquisition of habitual bipedal walking in hominins.

Early social adversity modulates the relation between attention biases and socioemotional behaviour in juvenile macaques

Affect-biased attention may play a fundamental role in early socioemotional development, but factors influencing its emergence and associations with typical versus pathological outcomes remain unclear. Here, we adopted a nonhuman primate model of early social adversity (ESA) to: (1) establish whether juvenile, pre-adolescent macaques demonstrate attention biases to both threatening and reward-related dynamic facial gestures; (2) examine the effects of early social experience on such biases; and (3) investigate how this relation may be linked to socioemotional behaviour. Two groups of juvenile macaques (ESA exposed and non-ESA exposed) were presented with pairs of dynamic facial gestures comprising two conditions: neutral-threat and neutral-lipsmacking. Attention biases to threat and lipsmacking were calculated as the proportion of gaze to the affective versus neutral gesture. Measures of anxiety and social engagement were also acquired from videos of the subjects in their everyday social environment. Results revealed that while both groups demonstrated an attention bias towards threatening facial gestures, a greater bias linked to anxiety was demonstrated by the ESA group only. Only the non-ESA group demonstrated a significant attention bias towards lipsmacking, and the degree of this positive bias was related to duration and frequency of social engagement in this group. These findings offer important insights into the effects of early social experience on affect-biased attention and related socioemotional behaviour in nonhuman primates, and demonstrate the utility of this model for future investigations into the neural and learning mechanisms underlying this relationship across development.

The effects of positive and negative experiences on subsequent behavior and cognitive performance in capuchin monkeys (Sapajus [Cebus] apella).

Our understanding of animals' affective processing is notably limited compared to the wealth of research on humans, largely due to difficulties in measurement. Moreover, despite a recent increase in the understanding of the interaction between affect and cognition in animals, most research has focused on negative affect, with the result that we continue to know little about the effects of positive affect. In this study, we tested 15 adult capuchin monkeys (Sapajus [Cebus] apella) using a novel methodology that took advantage of capuchins' species-typical behavior to engineer both a positive and negative experience, using the same apparatus to minimize extraneous impacts. Following a positive or negative experience (that presumably induced positive and negative affect, respectively), or a control with no manipulation, we assessed subjects' performance on a cognitive task, a computerized delayed match-to-sample. As predicted, behavior following the negative condition suggested a negative affective state, with increased rates of scratching (commonly used as an indicator of stress in nonhuman primates) compared to both the positive and control conditions. Cognitive performance was also impaired in the negative condition compared to the other two. Contrary to predictions, however, the positive condition did not have a facilitative effect on cognitive performance, but behavioral results indicate that we may not have induced a truly positive affective state. Although we add to evidence that a negative experience can influence subsequent behavior and cognitive performance in nonhuman primates, our work highlights our lack of knowledge about the impact of positive affect, if any, on behavior and cognition. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Application of non-human primates’ behavioral research in the study of spinal cord injury

<p indent="0mm">With the rapid development of therapeutic research on spinal cord injury (SCI), more and more basic research results are beginning to be translated to the clinic. Non-human primates have similar gene sequences and neuroanatomical structures to humans and are therefore widely used in the preclinical translational phase of SCI. Behavioral assessment is one of the most important tools used in SCI research and has been applied in almost all related studies, providing an important reference for evaluating the effectiveness of therapies. The rapid advances in the study of behaviors in non-human primates have enabled the evolution of behavioral assessments from single, crude tests to sophisticated and refined observations. In this context, a growing number of relevant experiments have analyzed the changes in the extent of SCI and the efficacy of related interventions through behavioral assessments in non-human primates. Based on the unique spinal descending control pathways and motor abilities of non-human primates, this paper reviews the use of different behavioral assessments in SCI, analyzes the deficiencies of existing tests, and points out some future directions.

Injections of AAV Vectors for Optogenetics in Anesthetized and Awake Behaving Non-Human Primate Brain.

Optogenetic techniques have revolutionized neuroscience research and are poised to do the same for neurological gene therapy. The clinical use of optogenetics, however, requires that safety and efficacy be demonstrated in animal models, ideally in non-human primates (NHPs), because of their neurological similarity to humans. The number of candidate vectors that are potentially useful for neuroscience and medicine is vast, and no high-throughput means to test these vectors yet exists. Thus, there is a need for techniques to make multiple spatially and volumetrically accurate injections of viral vectors into NHP brain that can be identified unambiguously through postmortem histology. Described herein is such a method. Injection cannulas are constructed from coupled polytetrafluoroethylene and stainless-steel tubes. These cannulas are autoclavable, disposable, and have low minimal-loading volumes, making them ideal for the injection of expensive, highly concentrated viral vector solutions. An inert, red-dyed mineral oil fills the dead space and forms a visible meniscus with the vector solution, allowing instantaneous and accurate measurement of injection rates and volumes. The oil is loaded into the rear of the cannula, reducing the risk of co-injection with the vector. Cannulas can be loaded in 10 min, and injections can be made in 20 min. This procedure is well suited for injections into awake or anesthetized animals. When used to deliver high-quality viral vectors, this procedure can produce robust expression of optogenetic proteins, allowing optical control of neural activity and behavior in NHPs.

Effects of music stimulus on behavior response, cortisol level, and horizontal immunity of growing pigs.

An enriched environment is widely used to improve domestic animals' welfare and promote their natural behaviors. Music can reduce abnormal behavior in humans, nonhuman primates, and rodents. However, little is known about the effects of music on pigs. This study aims to explore the effects of repeated music stimulation on the behavior, physiology, and immunity of growing pigs. A total of 72 hybrid piglets (Large White × Duroc × Minpig) were randomly divided into three groups, including music (Mozart K.448, 60 to 70 dB), noise (recorded mechanical noise, 80 to 85 dB), and control (natural background sound, <40 dB), and 6 h sound stimulation was given per day (1000 to 1600 hours) from 40 to 100 d of age. The behavioral activities of the pigs were observed during the music stimulation, and their serum cortisol, salivary cortisol, and serum immune indices were also measured. Compared with the control group, the music group and noise group increased activity but decreased lying of pigs (P < 0.05). A significant increase in tail-wagging, playing, and exploring behaviors of pigs was found in the music group (P < 0.05), and the noise significantly increased the aggressive behavior of the pigs (P < 0.05). Tail-wagging, playing, exploring, manipulating, and aggressive behaviors decreased over time. Short-term (8 d) music stimulus had a lower cortisol level than that of the noise and control groups (P < 0.05), whereas long-term (60 d) music stimulus increased immunoglobulin G (IgG), interleukin-2 (IL-2), and interferon-gamma (IFN-γ) levels (P < 0.05) and decreased interleukin-4 (IL-4) level (P < 0.05). Long-term noise stimulus significantly reduced the level of IgG (P < 0.05) but did not affect the level of IL-2, IL-4, and IFN-γ levels (P > 0.05). In conclusion, short-term music stimulus (8 d) reduced the stress response, whereas long-term music stimulus (60 d) enhanced the immune responses. In addition, the noise increased the aggressive behavior, and long-term noise reduced the immunity of the growing pigs.

Effects of 3,4‐methylenedioxymethamphetamine (MDMA) and d‐methamphetamine on pro‐social behavior in drug‐naïve female nonhuman primates

Previous preclinical studies have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) dose-dependently increases pro-social behavior and affiliative vocalizations in male nonhuman primates. As diagnostic criteria for several psychiatric diseases includes deficits in social functioning, examining the conditions under which MDMA selectively increases pro-social behavior may provide important insights into MDMA's potential as a therapeutic. One such condition is whether a subject's drug history has any impact on MDMA's ability to modulate social behavior. Here, we examined the ability of MDMA and d-methamphetamine (MA) to modulate pro-social behavior and affiliative vocalizations in four pairs of drug-naïve female squirrel monkeys (n=8). Doses of MDMA (0.1-1.0 mg/kg), MA (0.03-0.3 mg/kg) or saline vehicle were administered 10-min prior to observation sessions in which pro-social behavior (huddling, touching, and sitting within proximity to each other) was scored by a blind observer. Vocalizations were recorded and spectrograph analyses were used to characterize vocalizations as either affiliative or aggressive. Results show that MDMA dose-dependently increased pro-social behavior, with 1.0 mg/kg eliciting the highest pro-social scores in comparison to saline, whereas the dopamine-preferring releaser MA elicited little pro-social behavior in comparison to saline. In contrast, both MDMA and MA dose-dependently decreased all measures of vocalizations in females, with the highest total number of vocalizations evident after 0.1 mg/kg MDMA and the lowest total number of vocalizations evident at 1.0 mg/kg MDMA. Aggressive vocalizations were not elicited by either MDMA or MA. These results corroborate previous findings that MDMA, but not d-MA, increases pro-social behavior in male subjects and extends them to females. However, MDMA's increase in pro-social behavior appears to be de-coupled from vocalizations in drug-naïve female subjects. These data are in contrast to other reports in male subjects with drug histories showing that MDMA dose-dependently increases affiliative behavior and vocalizations. Taken together, these results suggest that sex and drug-history may be important variables in considering MDMA's efficacy in increasing pro-social behavior. Future studies will include drug naïve male subjects to investigate sex as a biological variable as well as other drugs that vary in selectivity for dopamine or serotonin release.

Prenatal Androgen Effects as a Proximate Mechanism Underpinning Variation in Social Behavior Among Female Nonhuman Primates

While the role of ecological factors in shaping primate social systems has been a central focus for decades, less attention has been given to phylogenetic relationships and the potential role of underlying proximate mechanisms. This study aimed to investigate the relationship between one such proximate mechanism, prenatal androgen effects (PAEs), and aspects of social behavior in female nonhuman primates using the 2D:4D ratio as a proxy for PAEs and phylogenetically controlled methods. In general, female 2D:4D ratios were highest in monogamous species (low inferred PAEs) and lowest in polygynandrous and polygynous species (high inferred PAEs). 2D:4D ratios also varied with the form of polygyny/polygynandry, potentially with regard to the need for competitive over cooperative behaviors and the intensity of female reproductive competition. Species characterized by female dominance had lower 2D:4D ratios than species characterized by male dominance or codominance. There were no significant relationships between 2D:4D ratio and either degree of frugivory or group size. Relationships between 2D:4D ratios and the directional consistency index and 2D:4D ratios and rates of female–female agonism were also nonsignificant although sample sizes for both of these variables were small. Female social relationships are a manifestation of complex competitive and cooperative behaviors and the results suggest that PAEs may act as a proximate mechanism underlying the expression of certain aspects of behavior in female primates in ways that are adaptive to their social system.

Effects of daily Δ9-Tetrahydrocannabinol (THC) alone or combined with cannabidiol (CBD) on cognition-based behavior and activity in adolescent nonhuman primates

BackgroundDaily use of marijuana is rising in adolescents, along with consumption of high potency marijuana products (high % Δ-9-tetrahydrocannabinol or THC). These dual, related trends have opened gaps in understanding the long-term effects of daily consumption of a high dose of THC in adolescents and whether a therapeutic dose of cannabidiol (CBD) modulates THC effects. MethodsAdolescent squirrel monkeys (Saimiri boliviensis) were treated daily for four months with vehicle (n = 4), a high THC dose (1 mg/kg i.m.; n = 4), or THC + CBD (1 mg/kg +3 mg/kg i.m.; n = 4), to investigate whether: (1) a daily high THC dose affects performance in tasks of cognition (repeated acquisition, discrimination reversal); (2) a daily high THC dose affects spontaneous behavior and day/night activity (3) tolerance develops to the behavioral effects of THC; (4) whether CBD modulates THC effects. ResultsTHC impaired performance of adolescent monkeys in a cognitive test initially, but not performance on a task of cognitive flexibility. THC reduced motor activity and increased sedentary behavior, with tolerance developing after weeks of daily treatment. Co-administered with THC, CBD did not modulate THC effects on cognitive performance, activity or tolerance, but prevented THC-induced emesis on the first day of daily treatment. ConclusionsDaily high dosing with THC compromised performance on a task of cognition, and reduced activity in adolescent primates, with tolerance developing within weeks. Whether our observations are relevant to a broader range of cognitive tasks vital for daily function in human adolescents is uncertain.