Inhibition of the LH Surge by Restraint Stress in Cyclic Rats: Studies on the Role of GABAA and GABAB Receptors

There is evidence that stress can alter the activity in the brain of gamma-aminobutyricacid (GABA), a neurotransmitter that has been implicated in the regulation of LH secretion. In the present study the role of GABA in the restraint stress-induced inhibition of the LH surge was investigated in the intact cyclic rat. Intracerebroventricular (icv) administration of the GABAA receptor agonist muscimol (0.1, 0.5 or 1 μg) 5 min before the presumed onset of the pro-oestrous LH surge (at 0900 h) caused a dose dependent suppression of the surge. A single dose of the GABAB receptor agonist baclofen (1 μg; icv) injected at 0855 h postponed the onset of the LH surge, and repeated injections at 0855 and 1130 h suppressed the surge. These data indicate that GABA-ergic activity in the brain can inhibit the LH surge in the cyclic rat via GABAA and GABAB receptors. Pro-oestrous rats were subjected to 5 hrs of restraint starting at 0855 h. Pretreatment with the GABAA receptor antagonist bicuculine (1 μg; icv) at 0840, 0940 and 1040 h or pretreatment with the GABAB receptor antagonist phaclofen (10 μg; icv) at 0840 h were ineffective in preventing the restraint-induced inhibition of the LH surge. The results suggest that GABAA and GABAB receptors are not involved in the inhibitory effect of restraint stress on the LH surge.     

Effects of Acute Stress or Centrally Injected Interleukin-1beta on Neuropeptide Expression in the Immune System

Acute stress stimulates the expression and release of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from the hypothalamus, and the pro-opiomelanocortin products beta-endorphin and ACTH from the anterior pituitary. These neuropeptides are also expressed in immune tissues, and it has been proposed that they may modulate immune responses to stress through paracrine mechanisms. We subjected rats to restraint stress or central injection of interleukin (IL)-1beta to determine whether these acute stimuli can alter the expression of neuropeptides in the spleen and thymus. Restraint stress significantly increased the contents of all these neuropeptides in thymic, but not splenic, extracts. A single icv injection of IL-1beta increased contents of CRH, AVP, ACTH and beta-endorphin in the spleens of both sham-operated and adrenalectomised (ADX) rats. IL-1beta increased thymic contents of CRH and ACTH in sham-operated rats but these increases were not observed in ADX rats. These results suggest that the effects of IL-1beta on neuropeptide expression in the spleen are independent of glucocorticoids, whereas IL-1beta stimulation of neuropeptide expression in the thymus is dependent on circulating glucocorticoids. There were significant correlations between increases in CRH, ACTH and beta-endorphin in the spleen, and between CRH and ACTH in the thymus, consistent with the suggestion that IL-1beta-induced increases in ACTH and beta-endorphin may be mediated through CRH. These results provide evidence that stressors can directly influence neuropeptide expression in immune tissues. Thus stress may influence immune functions through paracrine mechanisms involving locally synthesised neuropeptides as well as through activation of the hypothalamo-pituitary-adrenal axis.     

Beyond heritability: neurotransmitter genes differentially modulate visuospatial attention and working memory

A cued, visuospatial attention task and a working memory task were administered to 89 healthy adults genotyped for a T-to-C polymorphism in CHRNA4, a nicotinic receptor subunit gene. Increasing gene dose of the C allele of the CHRNA4 gene (i.e., no C alleles, one C allele, two C alleles) was associated with increased reaction time (RT) benefits of valid attentional cuing and reduced RT costs of invalid cues, but was not associated with working memory performance. In a second experiment, 103 healthy persons were genotyped for a G-to-A polymorphism of the dopamine beta-hydroxylase (DBH) gene. Increasing gene dose of the G allele of the DBH gene was associated with increased working memory accuracy at a high memory load. However, there was no consistent association between the DBH gene and visuospatial attention. Thus, a double dissociation was observed, with visuospatial attention associated with CHRNA4 but not the DBH gene and, conversely, working memory associated with the DBH gene but not CHRNA4. The results show that normal allelic variations in single neurotransmitter genes modulate individual differences in processing components of cognitive functions in healthy individuals.     

COMT genotype influences prefrontal response to emotional distraction

Early studies of genetic effects on brain activity have been conducted to investigate primarily either the influence of polymorphisms in dopaminergic genes, especially the catechol-O-methyltransferase (COMT) gene, on prefrontal cognitive processes such as working memory, or that of polymorphisms in the serotonin transporter gene on the amygdala response to threatening stimuli. Here, we address genetic influences on the neural systems underlying cognitive-affective interactions. Specifically, we assess the effect of the COMT val¹⁵⁸met polymorphism on frontal regulation of attention under emotional distraction. Healthy volunteers were scanned while performing a house-matching task with affectively negative versus neutral distractors. Effects of val allele load were examined on frontal regions associated with attentional control and emotion regulation, and on parahippocampal regions associated with perception of houses. As we predicted, val load correlated positively with activity in control- and task-related regions during performance under emotional distraction. These findings provide an initial step toward identifying genetic contributions to interindividual variability in recruitment of mechanisms that regulate affective processing.     

大学二年级学生人际宽恕与报复心理及其与抑郁的关系研究

采用沉思量表、报复动机量表、宽恕倾向量表、宽恕态度量表和流调中心用抑郁量表对236名大二学生进行问卷调查,综合探讨大学生人际宽恕和报复心理及其与抑郁的关系。研究发现:(1)男大学生的报复倾向显著高于女大学生。(2)宽恕倾向与报复倾向及对侵犯的沉思程度显著负相关。沉思程度和抑郁显著正相关。(3)沉思程度和宽恕倾向对抑郁分别具有显著的正向和负向的预测作用。(4)大学生的宽恕倾向和宽恕态度的相互作用以及宽恕倾向和报复倾向之间的交互作用对抑郁均没有显著预测作用。     

Genes, brain, and behavior: Bridging disciplines

With excitement surrounding the publication of the human genome, scientists have set out to uncover the functions of specific genes. This special issue on Genes, Brain, and Behavior attempts to present research strategies that connect major avenues of genetic research across disciplines. For example, anatomical information provided by brain imaging can serve as a convenient link between anatomical abnormalities seen in knockout/transgenic mouse models and abnormal patterns of brain activity seen in certain patient populations. Identifying genetic risk factors for disorders with carefully designed cognitive assays is another strategy that has gained increasing attention. These approaches are being combined with behavioral studies of mouse models of gene function. Alone, each of these approaches provides limited information on gene function in complex human behavior, but together, they are forming bridges between animal models and human psychiatric disorders.     

Synaptogenesis and heritable aspects of executive attention

In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development. Of particular interest is the development of executive function, which develops more gradually in humans. One approach that has shown promise is molecular genetics. The completion of the human genome project and the human genome diversity project make it straightforward to ask whether variation in a particular gene correlates with variation in behavior, brain structure, brain activity, or all of the above. Strategies that unify the wealth of biochemical knowledge pertaining to synapse formation with the functional measures of brain structure and activity may lead to new insights in developmental cognitive psychology.     

Evaluation of a structural polymorphism in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activation of executive attention networks

The specificity of genetic effects on brain activation is a central issue in understanding how molecular actions at the synapse relate to anatomic patterns of brain activity. In an effort to understand the basis for the specificity of gene-associated brain activity, we explore a well-studied genetic polymorphism, TaqIA, which lies downstream of the DRD2 gene in the protein-encoding region of a neighboring gene, ANKK1, which is not expressed in the brain. We utilize the attention network test and find that carriers of the A1 allele show gene-associated functional activation in an anatomically specific, dopamine-rich region of the brain comprising the anterior cingulate gyrus, a finding partially consistent with prior data from functional imaging genetics. A review of the patterns of expression for ANKK1 and DRD2 and the extent of linkage disequilibrium between the two genes sheds light on additional criteria for the selection of candidate genes in imaging-genetic studies.     

Information processing bias against emotional facial expressions in social anxiety

The present study examined whether information processing bias against emotional facial expressions is present among individuals with social anxiety. College students with high (high social anxiety group; n  = 26) and low social anxiety (low social anxiety group; n  = 26) performed three different types of working memory tasks: (a) ordering positive and negative facial expressions according to the intensity of emotion; (b) ordering pictures of faces according to age; and (c) ordering geometric shapes according to size. The high social anxiety group performed significantly more poorly than the low social anxiety group on the facial expression task, but not on the other two tasks with the nonemotional stimuli. These results suggest that high social anxiety interferes with processing of emotionally charged facial expressions.