Stress plays an important role in psychiatric disorders, and preclinical evidence indicates that the central endocannabinoid system modulates endocrine and neuronal responses to stress. This study aimed to investigate the effect of acute stress on circulating concentrations of endocannabinoids (eCBs) in healthy humans. A total of 71 adults participated in two sessions in which they were exposed to either a standardized psychosocial stress procedure (Trier Social Stress Test) or a control task. Blood samples for eCB and cortisol assays and cardiovascular and subjective measures were obtained before and at regular intervals after the tasks. Serum concentrations of the eCBs, N-arachidonylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), as well as of the N-acylethanolamides (NAEs), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), and of the O-acylglycerol, 2-oleoylglycerol (2-OG), were determined. Compared with the control condition, stress increased serum concentrations of AEA and the other NAEs immediately after the stress period. Increases in PEA were positively correlated with increases in serum cortisol after stress. Furthermore, anxiety ratings at baseline were negatively correlated with baseline concentrations of AEA. The sex and menstrual cycle status of the subject affected the NAE responses to stress. Interestingly, subjects of Asian and African-American races exhibited different patterns of stress responses compared with the Caucasian subjects. These results indicate that stress increases circulating NAEs in healthy human volunteers. This finding supports a protective role for eCBs in anxiety. Further research is needed to elucidate the function of these lipid mediators, and to determine the mechanisms that regulate their appearance in the circulation.

The prevalence of stress disorders differs between men and women. An understanding of how men and women vary in acute stress responses may help to understand these sex differences. We compared responses to the TSST and a control task in healthy men (N=28) and women tested in two phases (Follicular N=29, Luteal N=23) of the menstrual cycle. Men exhibited greater cortisol responses to stress than women in either phase. Luteal women exhibited the greatest subjective and allopregnanolone responses to stress, whereas follicular women exhibited blunted noradrenaline responses. Partial correlations controlling for group differences revealed that individuals who were most sensitive to the subjective effects of stress exhibited the largest salivary cortisol, noradrenaline, and allopregnanolone responses and the smallest progesterone responses to stress. We discuss our findings in the context of sex differences in the prevalence of stress-linked disorders.

The dopamine D2 receptor (DRD2) appears to be involved in impulsive behaviors, and particularly in behavioral inhibition. We sought to determine whether inhibition and impulsivity were related to genetic polymorphisms in the DRD2 gene (DRD2) in healthy volunteers (N = 93). Participants received placebo or d-amphetamine in random order. They performed the stop task, measuring behavioral inhibition, and rated their mood states on each session. They also completed the Zuckerman-Kuhlman Personality Questionnaire, including an Impulsivity subscale. We investigated the association between 12 single nucleotide polymorphisms (SNPs) and haplotypes in DRD2 and stop task performance in the nondrug (i.e., placebo) session and on the personality measure of impulsivity. We secondarily evaluated the DRD2 SNPs in relation to response to d-amphetamine on stop task performance and mood ratings. Mood was not related to genotypes in either the drug free condition or in response to drug. However, 2 SNPs, rs4648317 and rs12364283, and a haplotype block consisting of those SNPs, were associated with better performance on the stop task in the drug free condition and lower scores on the Impulsivity subscale. We also found that rs12364283 was associated with effects of d-amphetamine on stop task performance: d-amphetamine decreased stop reaction time (RT) in the A/A group but increased stop RT in the combined A/G + G/G genotype. Of the SNPs we evaluated, rs12364283, which has been associated with DRD2 expression, was the most significantly associated with inhibition and impulsivity. The significant relationship between DRD2 genotype and both behavioral inhibition and impulsivity suggests a possible common genetic influence on behavioral and self-report measures of impulsivity. Keywords DRD2; inhibition; impulsivity; amphetamine; Stop TaskIndividuals vary in behavioral inhibition, or the predisposition to respond to stimuli without regard to negative consequences. These individual differences have been observed in healthy populations (de Wit, Crean, & Richards, 2000), as well as in psychiatric samples such as patients with attention deficit/hyperactivity disorder and substance use disorders (Colzato, van Correspondence concerning this article should be addressed to Harriet de Wit, Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 5841 South Maryland Avenue, MC3077, Chicago, IL 60637. hdew@uchicago.edu. & Hommel, 2007;Schachar, Tannock, & Logan, 1993). One possible source of the observed variability is genetic variation in the neurotransmitter systems responsible for the phenotype. Several lines of evidence suggest that dopamine plays an important role in inhibition in both humans (Friedel, 2004) and nonhumans (Cardinal, Pennicott, Sugathapala, Robbins, & Everitt, 2001;Dulawa, Grandy, Low, Paulus, & Geyer, 1999;Puumala, & Sirvio, 1998;Rubinstein et al., 1997;Winstanley, Theobald, Cardinal, & Robbins, 2004. Specifically, there is evidence that the dopamine receptor D2 (DRD2) is important for inhibi...

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