Distribution of thyrotrophin-releasing hormone receptor messenger RNA in rat pituitary and brain

X-ray diffraction methods have been used to determine the structure of the 8.3 kDa hydrophobic protein from soybean and to refine the atomic co-ordinates to a crystallographic R-factor of 18.7% at 1.8 A resolution. The molecule is a four-helix bundle, which together with the connecting loops and a twisted beta-strand form a spiral. The surface contains 70% apolar atoms, and the crystal packing is dominated by hydrophobic interactions, producing a two-dimensional sheet of protein molecules. Most of the 59 water molecules located are involved in hydrophilic contacts and their structural organization does not seem to be affected by the high hydrophobicity of the molecule. From the protein fold it appears that three of the four disulphide bridges are important for keeping the amino and carboxyl-terminal segments in place in the native form, while the central part of the molecule is stabilized by many hydrophobic interactions. Although the protein function is not known, a number of possibilities can be excluded on experimental grounds and by comparison with other members of the family.     

Effect of thyrotropin-releasing hormone on secretion of thyrotropin, prolactin, thyroxine, and triiodothyronine in pregnant and fetal rhesus monkeys

The effect of thyrotropin-releasing hormone (TRH) on the pituitary-thyroid axis and on prolactin secretion was studied in pregnant Rhesus monkeys during the latter period of gestation and in non-pregnant female controls. The baseline plasma concentrations of TSH, T3, T4, and prolactin (PRL) of pregnant monkeys did not differ from those of non-pregnant monkeys. After administration of TRH, plasma prolactin rose to higher levels in pregnant monkeys than in non-pregnant monkeys whereas there was a similar response of plasma TSH, T4 and T3 in both groups. The baseline plasma TSH was elevated and plasma T3 was decreased in the fetus compared with the mother. Administration of TRH iv to the maternal monkey caused a larger response in the fetal plasma TSH than in that of the mother and was followed by larger increments in plasma T4 and T3 concentrations in the fetuses than in the mothers. The larger increments of plasma TSH and thyroid hormones in the fetus compared with the mother also occurred when TRH was given iv to the fetus. There was a significant rise of plasma prolactin in both mother and fetus after administration of TRH to mother or fetus; the increase of plasma PRL was much higher in the mother than in the fetus. The data show that TRH can cross the primate placenta in either the maternal to fetal or fetal to maternal direction. The fetal thyroid of the Rhesus monkey during the latter period of gestation can release both T4 and T3 in response to TSH.     

Somatostatin at low doses stimulates growth hormone release from intact cultures of porcine pituitary cells

Somatostatin (SRIF) is the primary inhibitory factor in the control of growth hormone (GH) release from somatotropes. This concept emerged from studies based mainly on the rat and human model. However, recent data suggest that the role of SRIF in the regulation of pituitary GH release might be different in other species such as the pig. Thus, in previous studies, we have demonstrated a dual (stimulatory/inhibitory) effect of SRIF on GH secretion in vitro in two porcine somatotrope subpopulations. In the present study, we have investigated whether SRIF can act as a GH-releasing factor in intact cultures of porcine somatotropes. To this end, both dose-related effects of SRIF on basal GH release and its effects on GH-releasing factor (GRF-)stimulated GH secretion were evaluated in monolayer cultures of porcine pituitary cells. SRIF did not affect basal secretion at the highest doses tested (10(-5), 10(-7), and 10(-9) M), whereas it induced a significant increase in GH secretion when applied at low doses (10(-11), 10(-13), and 10(-15) M). High-dose (10(-7) M) SRIF significantly reduced GRF-induced GH secretion, an effect that was absent at the lowest dose (10(-15) M) of the peptide tested. These results confirm the dual role af SRIF on GH secretion from porcine somatotropes, and demonstrate that SRIF, at low doses, can act as a true GH-releasing factor.     

Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures

Predictions of the minimal size an organism must have to swim along stimulus gradients were used to compare the relative advantages of sensory systems employing spatial (simultaneous) and temporal (sequential) gradient detection mechanisms for small free-swimming bacteria, leading to the following conclusions: 1) there are environmental conditions where spatial detection mechanisms can function for smaller organisms than can temporal mechanisms, 2) temporal mechanisms are superior (have a smaller size limit) for the difficult conditions of low concentration and shallow gradients, but 3) observed bacterial chemotaxis occurs mostly under conditions where spatial mechanisms have a smaller size limit, and 4) relevant conditions in the natural environment favor temporal mechanisms in some cases and spatial mechanisms in others. Thus, sensory ecology considerations do not preclude free-swimming bacteria from employing spatial detection mechanisms, as has been thought, and microbiologists should be on the lookout for them. If spatial mechanisms do not occur, the explanation should be sought elsewhere.     

Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood

Monocyte chemotactic peptide-1 (MCP-1) belongs to a large family of cytokines known as chemokines. It is a potent mediator of inflammatory response and is thought to play a major role in recruiting monocytes into the site of inflammation. Mixed cryoglobulinemia is a systemic vasculitis characterized in 10 to 30% of the cases by renal involvement. Monocyte infiltration into the glomerulus, and in the periglomerular and perivascular areas is a common histopathological feature of this form of glomerulonephritis. We sought to determine, by in situ hybridization and immunohistochemistry, the renal gene and protein expression of MCP-1 in cryoglobulinemic glomerulonephritis compared to normal kidney, and to correlate it with macrophage infiltration. Kidney biopsy specimens were obtained from 9 patients with cryoglobulinemic glomerulonephritis and 9 control kidneys. The distribution and intensity of MCP-1 gene and protein expression, and the macrophage infiltration (CD68 positive cells) were evaluated and quantitated by a computerized image analysis system. In normal kidneys, MCP-1 was weakly expressed, both at the gene as well as at the protein level. In diseased kidneys, a statistically significant (P < 0.001) up-regulation of MCP-1 gene and protein expression was found, particularly within the areas of tubulointerstitial damage and the glomeruli. By means of CD68 positive cells, a significant correlation (P < 0.001) was found between glomerular, tubulointerstitial macrophage infiltration and MCP-1 expression. Moreover, by combining immunohistochemistry and in situ hybridization, we observed the presence of CD68 positive cells mainly, if not exclusively, around the cells expressing MCP-1 mRNA. Interestingly, a striking increase in MCP-1 urinary concentration was found in cryoglobulinemic patients. In conclusion, our data suggest that MCP-1 may play a major role in modulating the inflammatory process observed in cryoglobulinemic glomerulonephritis.     

Physiological roles of thyrotrophin-releasing hormone and vasoactive intestinal peptide on the pulsatile secretory patterns of prolactin in pituitary-grafted female rats

Much is known about the fact that thyrotrophin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulate prolactin secretion but areas of uncertainty remain. This work was undertaken to describe the effects of TRH and VIP on the pulsatile secretion pattern of prolactin, in adult sham-operated and pituitary-grafted hyperprolactinaemic female rats. Two pulses of TRH (1 microgram/rat) or one pulse of VIP (20 micrograms/rat) were given 60 or 120 min after the period of blood sampling. Pituitary grafting increased the mean values of prolactin, absolute amplitude and duration of the peaks and decreased their frequency, compared with control animals. In sham-operated rats, TRH elevated prolactin levels by increasing the absolute and relative amplitudes and duration of the pulses, along with a decrease in their frequency. No priming effects of TRH were observed in this study. Hyperprolactinaemia blunted TRH effects on the pulsatile secretion pattern of prolactin. In sham-operated rats, VIP administration increased the absolute and relative amplitudes of the prolactin peaks. None of the other parameters studied were changed. In pituitary-grafted animals, VIP administration increased the absolute and relative amplitudes of the prolactin peaks but to a lesser extent compared with controls. These data suggest that TRH and VIP affect prolactin pulsatility differentially. The effects of TRH and VIP were blunted to some extent by exposure to previously elevated circulating prolactin levels.     

Effects of large doses of estrogen on prolactin and growth hormone release

The effects of large doses of estrogen on prolactin (PRL) release were assessed. Circulating PRL levels in response to intravenous infusion of 17 beta-estradiol (E2), at a rate of 50 mug per hour for 4 hours, were studied in 10 subjects, and a chronic administration of ethinyl estradiol (EE) at a dose of 400 mug per day, for 1 week, was evaluated in five hypogonadal subjects. There was a significant depression of serum level of PRL during the E2 infusion and a significant increase in PRL release after discontinuation of the infusion. The chronic treatment of large doses of EE induced a more rapid (within 36 hours) and a significantly greater elevation of PRL levels at the end of 1 week treatment than those found during smaller doses of EE administration, as reported previously. These data suggest that acute treatment of estrogen may have a biphasic action on the pituitary PRL section and that the augmentatory effect of estrogen on PRL secretion is dose-dependent in human beings.     

Different behavior of lactotroph cell subpopulations in response to angiotensin II and thyrotrophin-releasing hormone

The low brachial and crural indices of the European Neandertals have long been considered indicative of cold adaptation. Recent work has documented lower limb/trunk ratios and deeper chests (anterior-posterior diameter) in European Neandertals than among their successors. The present study uses variables reflective of limb length, body mass and trunk height, and compares European Neandertals to 15 globally diverse recent human samples (1 "Eskimo," 3 North African, 4 sub-Saharan African and 7 European). Bivariate plots, as well as principal components analysis plots of log shape-transformed data, indicate that European Neandertals had an overall body shape that falls at the extreme end of modern higher latitude groups' range of variation. Cluster analysis (minimum spanning tree on a principal coordinates plot) indicates that the Neandertals are closest in body shape to modern "Eskimos," but even in this dendrogram, they are joined to the "Eskimo" via a long branch. In fact, it appears that European Neandertals were "hyperpolar" in body shape, likely due to two factors: 1) the extremely cold temperatures of glacial Europe and 2) less effective cultural buffering against cold stress.     

Annual variations in serum thyroid-stimulating hormone and thyroid hormones and in their responses to thyrotrophin-releasing hormone in the reindeer

The reindeer in its natural habitat is subject to great annual variations in ambient temperature, illumination and nutrition. To ascertain the effect of these environmental factors on thyroid function, serum thyroid-stimulating hormone (TSH), thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) concentrations were measured four times a year (2 June, 8 October, 21 November, and 24 February) in 14 animals housed outdoors at latitude 69 degrees 10'N. They all showed statistically significant (P < 0.05) seasonal changes. Serum TSH and T4 were highest in February (623 +/- 30 ng/ml and 287 +/- 19 nmol/l respectively). TSH was lowest in October (318 +/- 47 ng/ml) and T4 in November (199 +/- 19 nmol/l). The T3 concentration was highest in November (3.0 +/- 0.3 nmol/l) and lowest in June (1.8 +/- 0.2 nmol/l). In contrast, rT3 was highest in June (3.6 +/- 1.2 nmol/l) and lowest in November (1.9 +/- 0.6 nmol/l). Thus, there was an inverse relationship between T3 and rT3 (linear regression r = -0.406, P < 0.01). TSH, T4, T3 and rT3 responses to exogenous thyrotrophin-releasing hormone (synthetic TRH; 500 micrograms i.m.) were determined in ten animals. The magnitude of their response to TRH was significantly (P < 0.05) dependent on the time of year. When compared with the control level all the parameters rose significantly (P < 0.05). The greatest rise in serum TSH occurred in October (219 +/- 151%) and the smallest in February (66 +/- 53%).(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo electrochemical studies of dopamine overflow and clearance in the striatum of normal and MPTP-treated rhesus monkeys

Translational recruitment of maternal mRNAs is an essential process in early metazoan development. To identify genes required for this regulatory pathway, we have examined a collection of Drosophila female-sterile mutants for defects in translation of maternal mRNAs. This strategy has revealed that maternal-effect mutations in the cortex and grauzone genes impair translational activation and cytoplasmic polyadenylation of bicoid and Toll mRNAs. Cortex embryos contain a bicoid mRNA indistinguishable in amount, localization, and structure from that in wild-type embryos. However, the bicoid mRNA in cortex embryos contains a shorter than normal polyadenosine (poly(A)) tail. Injection of polyadenylated bicoid mRNA into cortex embryos allows translation demonstrating that insufficient polyadenylation prevents endogenous bicoid mRNA translation. In contrast nanos mRNA, which is activated by a poly(A)-independent mechanism, is translated in cortex embryos, indicating that the block in maternal mRNA activation is specific to a class of mRNAs. Cortex embryos are fertilized, but arrest at the onset of embryogenesis. Characterization of grauzone mutations indicates that the phenotype of these embryos is similar to cortex. These results identify a fundamental pathway that serves a vital role in the initiation of development.     

Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization

Various changes in the function of dopamine neurons have been proposed to underly the development of behavioral sensitization to the locomotor stimulant effects of d-amphetamine. The present study examined the relative importance of two such mechanisms after both short (3-4 days off) and longer (10-14 days off) withdrawals from repeated amphetamine or saline injection (1 mg/kg/day, days 1-5 and 8-12). First, single-unit recording was used to examine the sensitivity of impulse-regulating somatodendritic autoreceptors located on mesoaccumbens dopamine neurons in the rat ventral tegmental area. Second, in vivo microdialysis was used to examine the ability of amphetamine challenge to increase extracellular dopamine levels in the rat nucleus accumbens. Amphetamine-treated rats exhibited robust behavioral sensitization at both time points as compared to saline-treated rats. At 3 to 4 days off, autoreceptor subsensitivity was observed in the ventral tegmental area of amphetamine-treated rats, but there was no significant change in the ability of amphetamine to increase extracellular dopamine levels in nucleus accumbens. However, after 10 to 14 days off, autoreceptor subsensitivity was no longer observed, but amphetamine challenge resulted in a significantly greater increase in extracellular dopamine levels in amphetamine-treated as compared to saline-treated rats. These findings suggest that autoreceptor subsensitivity is a transient effect which may be related to the development of sensitization, whereas enhancement of amphetamine-stimulated dopamine release does not accompany early stages of behavioral sensitization, but may be involved in the persistence of the phenomenon after longer withdrawal periods.     

Co-localization of human growth hormone and human prolactin in hormonally pure human growth hormone-producing pituitary adenomas

Co-localization of human growth hormone (hGH) and human prolactin (hPRL) in hGH-producing pituitary adenomas was examined by electron microscopy with immunoblot analysis. At the electron microscopic level using anti-hGH or anti-hPRL polyclonal antibody, hGH and hPRL were found to be co-localized within each of the secretory granules in one of five cases. Double-labeling electron immunocytochemistry using colloidal gold particles of different sizes was effective in demonstrating this co-localization. As an additional step, we performed immunoblot analysis of hGH-producing pituitary adenomas using monoclonal antibodies. Four hGH-producing adenomatous tissue samples contained several hPRL-immunoreactive bands. In Case 2, the main 23K hPRL band was stained especially strongly The immunoblotting analysis of purified hGH using both anti-hPRL polyclonal antibody and monoclonal antibody to asses cross-reaction of the polyclonal anti-hPRL antisera with hGH revealed that both monoclonal and polyclonal antibodies were suitable for determining the co-localization. Double-labeling techniques using anti-hGH and anti-hPRL monoclonal antibodies demonstrated that only a few secretory granules were positive for co-localization of both hGH and hPRL (Case 2). The present study, which used not only polyclonal but also monoclonal antibodies, suggests that some hGH-producing pituitary adenomas contained both hPRL and hGH in the same secretory granules of tumor cells.     

GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys

Microdialysis measurements of dopamine (DA) and DA metabolites were carried out in the putamen and substantia nigra of unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rhesus monkeys that received intraventricular injections of vehicle or glial-derived neurotrophic factor (GDNF, 300 microg) 3 weeks prior to the microdialysis studies. Following behavioral measures in the MPTP-lesioned monkeys, they were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging (MRI)-guided sterile stereotaxic procedures were used for implantations of the microdialysis probes. Basal extracellular levels of DA and the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found to be decreased by >95% in the right putamen of the MPTP-lesioned monkeys as compared to normal animals. In contrast, basal DA levels were not significantly decreased, and DOPAC and HVA levels were decreased by only 65% and 30%, respectively, in the MPTP-lesioned substantia nigra. Significant reductions in d-amphetamine-evoked DA release were also observed in the MPTP-lesioned substantia nigra and putamen of the monkeys as compared to normal animals. A single intraventricular administration of GDNF into one group of MPTP-lesioned monkeys elicited improvements in the parkinsonian symptoms in these animals at 2-3 weeks post-administration. In addition, d-amphetamine-evoked overflow of DA was significantly increased in the substantia nigra but not the putamen of MPTP-lesioned monkeys that had received GDNF. Moreover, post-mortem brain tissue studies showed increases in whole tissue levels of DA and DA metabolite levels primarily within the substantia nigra in MPTP-lesioned monkeys that had received GDNF. Taken together, these data support that single ventricular infusions of GDNF produce improvements in motoric behavior in MPTP-lesioned monkeys that correlate with increases in DA neuronal function that are localized to the substantia nigra and not the putamen.     

Changes in mediobasal hypothalamic dopamine and GABA release: a possible mechanism underlying taurine-induced prolactin secretion

BACKGROUND: In the last years the interest for Informed Consent (IC) in anaesthesia has been growing and it has been debated on the adequate explanations in order to obtain a consent. The purpose of the present study was to assess patients' desire for information about anaesthesia. METHODS: In this prospective study a form has been given to consecutive patients waiting for surgical operation in general surgery or ear nose throat surgery and able to read and write, to inform them about the necessity of General Anaesthesia (GA); they were asked to complete a questionnaire concerning their desire for information about the following six items concerning anaesthesia: "the duration of anaesthesia"; "what type of pain will I have when I come round, and what pain-killers will I be given"; "details on the various types of anaesthesia, how and where will I be anaesthetized"; "what are the most common complications of general anaesthesia"; "where and how will I come round from general anaesthesia"; "what is artificial respiration in general anaesthesia". RESULTS: 107 patients participated in the study, 24 of whom were undergoing surgery for malignant cancer and 83 for benign non-oncological diseases. More than two-thirds of patients expressed their wish to receive information, and the trend of desire to know was inversely related to age (p < 0.05). There was no significant statistical difference in the desire to know according either to sex or to the kind of disease (benign or malignant). The demand for information about pain was particularly high (85%), also in the older group of patients. The results and the difficulties for obtaining IC are debated. CONCLUSIONS: The growth of patients' desire for information about anaesthesia is an aspect of the evolving doctor-patient relationship in Italy. Efforts should be directed at improving reciprocal communication.     

Abnormal behavior in relation to cage size in rhesus monkeys.

Rhesus monkeys (Macaca mulatta) either of wild origin or mother-reared in the laboratory were housed along in small caged from birth to 6? yrs. Observations were made on 24 Ss that were introduced singly into a small and a large test cage. Both the laboratory mother-reared and the wild-reared Ss showed abnormal behavior. The extent of the normal behavior repertoire was not smaller in Ss showing a relatively large degree of abnormal behavior. In a large cage, more normal but less stereotyped locomotion was shown than in a small cage. However, nonlocomotory abnormal patterns were not influenced by cage dimensions. The various abnormal behaviors were randomly associated. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Angiotensinergic neurons physiologically inhibit prolactin, growth hormone, and thyroid-stimulating hormone, but not adrenocorticoptropic hormone, release in ovariectomized rats

Angiotensin II (AII)-containing neurons with cell bodies in the rostral medial hypothalamus and axons project to the external layer of the median eminence, so that AII maybe released into the hypophyseal portal vessels for actions on the pituitary gland. Indeed, intrahypothalamic actions of the peptide on the release of hypothalamic hormones and direct actions on the pituitary have been reported. To determine the role of endogenously released AII in hypothalamic-pituitary hormone release, we have determined the effects of central immunoneutralization of AII upon the plasma concentrations of prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and adrenocorticotropic hormone (ACTH). Specific antiserum directed against AII (AB-AII) or normal rabbit serum (NRS), as a control, was microinjected into third ventricular (3 V) cannulae of conscious, ovariectomized (OVX) rats. Immediately before and at various intervals after this procedure, blood samples were withdrawn through previously implanted external jugular catheters. Three hours after injection of the AB-AII, plasma PRL levels diverged from those of the NRS-injected animals and progressively increased from 4 to 24 h after administration of the antiserum. Results were similar with respect to plasma GH, except that the increase in the AB-AII animals above that in the NRS-injected controls from 4 to 6 h was not significant, but was highly significant on measurement 24 h after injection, at which time plasma GH was three times higher than in control rats. Similarly, following injection of AB-AII, plasma TSH values did not diverge significantly from those of the NRS-injected controls until 3 h after injection. From 3 to 5 h they remained constant and significantly elevated above values in the NRS-injected controls with a further nonsignificant increase at 6 h. At 24 h, there was no longer a difference between the values in both groups. In contrast to the significant elevations in plasma hormone levels observed with respect to PRL, GH, and TSH following injection of the antiserum, there was no change in plasma ACTH between the AB-AII-injected and NRS-injected animals throughout the same period of observation. Previous results by others have shown that intraventricular injection of AII has a suppressive action on the release of PRL, GH, and TSH. Consequently, we believe that the antiserum is acting intrahypothalamically to block the action of AII within the hypothalamus, resulting in the elevation of the three hormones mentioned. Therefore, the AII neurons appear to have a physiologically significant suppressive action on the release of hypothalamic neurohormones controlling the release of PRL, GH, and TSH. In contrast, there apparently is no effect of intrahypothalamically released AII on the secretion of corticotropin-releasing factors under these nonstress conditions. We cannot rule out an action of the antiserum at the pituitary level; however, in view of the fact that the actions of AII directly on the gland are to stimulate PRL, GH, TSH, and ACTH release, it appears that the antiserum was acting at the hypothalamic level.     

Face scanning and responsiveness to social cues in infant rhesus monkeys.

Investigated the development of gaze aversion in 8 infant rhesus monkeys (Macaca mulatta) by recording their visual fixations while they scanned pictures of monkey faces looking back at them and pictures of monkey faces looking away. During the 1st week of life, Ss inspected the 2 face-types equally. During Weeks 3 and 7, however, they inspected the faces looking back less than the faces looking away. The maturation of selective viewing was not paralleled by changes in scanning strategies (e.g., by a shift from scanning the contours of faces to fixations of internal details). The implications of early species-typical social awareness for social and perceptual development in rhesus monkeys are discussed. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thyrotropin-releasing hormone affects the oxytocin, vasopressin and prolactin release in female rats during midlactation: relation to suckling

The effect of thyrotropin-releasing hormone (TRH; 200 ng i.c.v.) on oxytocin (OT), vasopressin (AVP) and prolactin (PRL) release was estimated in female Wistar rats during midlactation. The hypothalamo-neurohypophysial radioimmunoassayed OT and AVP storage as well as blood plasma level of both neurohypophysial hormones and PRL in females suckled or not suckled have been studied. I.c.v. administration of TRH increased AVP content both in the hypothalamus and neurohypophysis of suckled females; however, plasma AVP level did not change. TRH increased the hypothalamic as well as neurohypophysial OT content during suckling. Simultaneously, TRH inhibited OT release into the blood plasma. On the contrary, in not suckled females TRH increased OT plasma concentration. I.c.v. TRH raised the PRL concentration in plasma of lactating but, at the moment, not suckled females. On the contrary, i.c.v. TRH injection into females just suckled was followed by a decrease in PRL plasma level. TRH probably acts in the central nervous system as an inhibitory neuromodulating factor for the vasopressin release. Also, it cannot be excluded that TRH--otherwise known to enhance the PRL release--suppresses the oxytocin-prolactin positive feedback mechanism when activated temporarily by suckling.     

Lateralized response to diazepam predicts temperamental style in rhesus monkeys.

Based on previous findings in humans and rhesus monkeys suggesting that diazepam has asymmetrical effects on frontal lobe activity and other literature supporting a role for the benzodiazepine system in the mediation of individual differences in anxiety and fearfulness, the relation between asymmetrical changes in scalp-recorded regional brain activity in response to diazepam and the temperamental dimension of behavioral inhibition indexed by freezing time in 9 rhesus monkeys was examined. Animals showed greater relative left-sided frontal activation in response to diazepam compared with the preceding baseline. The magnitude of this shift was strongly correlated with an aggregate measure of freezing time (r?=?.82). The implications of these findings for understanding the role of regional differences in the benzodiazepine system in mediating individual differences in fearfulness are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)