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Physiological and behavioral differences between dominant and subordinate monkeys have been useful in preclinical models investigating numerous disease states. In captivity, it has been inferred that subordinate monkeys live in a context of chronic social stress and may be at risk for a variety of dysfunctions; however, the factors that influence eventual rank are not entirely known. The goal of the present study was to first evaluate several phenotypic characteristics as potential trait markers for eventual social rank and then to determine the consequences of social hierarchy on these measures (i.e., state markers). Baseline estradiol, progesterone, cortisol and testosterone concentrations were obtained from 16 pair-housed female cynomolgus monkeys before and after introduction into new social groups ( n = 4/group). Furthermore, effects of the initial week of social rank establishment on outcome measures of cognitive performance and homecage activity were examined. Baseline body weight and mean serum estradiol concentrations were the only statistically significant predictors of eventual rank, with future subordinate monkeys weighing less and having higher estradiol concentrations. During initial hierarchy establishment, future subordinate monkeys had increased morning and afternoon cortisol concentrations, increased locomotor activity and impaired cognitive performance on a working memory task. After 3 months of social housing, subordinate monkeys had blunted circulating estradiol and progesterone concentrations. These findings demonstrate differential effects on gonadal hormones and cortisol as a function of social context in normally cycling female monkeys. Furthermore, disruptions in cognitive performance were associated with subordinate status, suggesting strong face validity of this model to the study of factors related to the etiology and treatment of human diseases associated with chronic stress. Am. J. Primatol. 78:402-417, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Identifying neurobiological characteristics that predict the development of cocaine use disorder would be of great value in prevention efforts. Because of their importance in mediating the abuse-related effects of cocaine, brain dopamine receptors are logical candidates for investigation. We analyzed data from two recently published studies that characterized availability of dopamine D2-like receptors (D2R) with [ 11 C]raclopride PET imaging and dopamine D 3 receptor (D 3 R) sensitivity with quinpirole-induced yawning in cocaine-naïve rhesus monkeys who subsequently acquired cocaine self-administration and completed a cocaine self-administration dose-effect curve. The present analysis compared D2R availability in several brain areas and characteristics of quinpirole-induced yawning, both acquired when monkeys were drug-naïve, with measures of initial sensitivity to cocaine. D2R availability in the caudate nucleus was negatively correlated with the ED 50 of the cocaine self-administration curve, although the significance of this relationship was driven by an outlier and was not present after the outlier was removed. No other significant associations were observed between D2R availability in any examined brain region and measures of sensitivity to cocaine reinforcement. However, there was a significant negative correlation between D 3 R sensitivity, represented by the ED 50 of the quinpirole-induced yawning curve, and the dose at which monkeys acquired cocaine self-administration. We also report no change from baseline D2R availability when a second PET scan was conducted after completion of the dose-effect curves. These data suggest the utility of D 3 R sensitivity, but not D2R availability, as a biomarker for vulnerability and resilience to cocaine. The well-established relationships between dopamine receptors and cocaine reinforcement in cocaine-experienced humans and animals may require extensive cocaine exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer's disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [ 11 C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [ 11 C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0-120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the "test" and "retest" data. [ 11 C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data ( r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [ 11 C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of such deficits remain unclear. Adult male rhesus monkeys ( N = 6) responded in the morning on tasks designed to assess different cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ 9 -tetrahydrocannabinol (THC; 0.01-0.56 mg/kg, i.v.) on cognitive performance, FR responding, and body temperature were determined. Next, THC (1.0-2.0 mg/kg, s.c.) was administered daily after FR 10 sessions for 12 weeks, during which the residual effects of THC (i.e., 22 hours after administration) on cognition were examined and the acute effects of THC were redetermined. In a subgroup of monkeys, dopamine D2/D3 receptor availability was assessed after 4 weeks of chronic THC exposure and compared with drug-naive controls using positron emission tomography and [ 11 C]-raclopride ( N = 4/group). Acute THC pretreatments dose-dependently decreased FR responding and body temperature, and impairment to cognitive performance was task specific. During chronic treatment, THC produced persistent residual impairment only to working memory; tolerance differentially developed to acute cognitive impairments. There was recovery from residual cognitive impairments to working memory within 2 weeks of abstinence. Compared with controls, D2/D3 receptor availability was not altered during chronic THC treatment. In conclusion, THC-induced disruptions in cognition were task-specific, as was tolerance development, and not related to changes in D2/D3 receptor availability. Intervention strategies for cannabis-use disorder that enhance working memory performance may facilitate positive treatment outcomes., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)

There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N = 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine self-administration dose-response curve was redetermined. In experiment 2, male monkeys (N = 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in low-dose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)