Long-Term Irrigation Affects the Dynamics and Activity of the Wheat Rhizosphere Microbiome.

The Inland Pacific Northwest (IPNW) encompasses 1. 6 million cropland hectares and is a major wheat-producing area in the western United States. The climate throughout the region is semi-arid, making the availability of water a significant challenge for IPNW agriculture. Much attention has been given to uncovering the effects of water stress on the physiology of wheat and the dynamics of its soilborne diseases. In contrast, the impact of soil moisture on the establishment and activity of microbial communities in the rhizosphere of dryland wheat remains poorly understood. We addressed this gap by conducting a three-year field study involving wheat grown in adjacent irrigated and dryland (rainfed) plots established in Lind, Washington State. We used deep amplicon sequencing of the V4 region of the 16S rRNA to characterize the responses of the wheat rhizosphere microbiome to overhead irrigation. We also characterized the population dynamics and activity of indigenous Phz+ rhizobacteria that produce the antibiotic phenazine-1-carboxylic acid (PCA) and contribute to the natural suppression of soilborne pathogens of wheat. Results of the study revealed that irrigation affected the Phz+ rhizobacteria adversely, which was evident from the significantly reduced plant colonization frequency, population size and levels of PCA in the field. The observed differences between irrigated and dryland plots were reproducible and amplified over the course of the study, thus identifying soil moisture as a critical abiotic factor that influences the dynamics, and activity of indigenous Phz+ communities. The three seasons of irrigation had a slight effect on the overall diversity within the rhizosphere microbiome but led to significant differences in the relative abundances of specific OTUs. In particular, irrigation differentially affected multiple groups of Bacteroidetes and Proteobacteria, including taxa with known plant growth-promoting activity. Analysis of environmental variables revealed that the separation between irrigated and dryland treatments was due to changes in the water potential (Ψm) and pH. In contrast, the temporal changes in the composition of the rhizosphere microbiome correlated with temperature and precipitation. In summary, our long-term study provides insights into how the availability of water in a semi-arid agroecosystem shapes the belowground wheat microbiome.

Phenazine-1-carboxylic acid and soil moisture influence biofilm development and turnover of rhizobacterial biomass on wheat root surfaces.

Phenazine-1-carboxylic acid (PCA) is produced by rhizobacteria in dryland but not in irrigated wheat fields of the Pacific Northwest, USA. PCA promotes biofilm development in bacterial cultures and bacterial colonization of wheat rhizospheres. However, its impact upon biofilm development has not been demonstrated in the rhizosphere, where biofilms influence terrestrial carbon and nitrogen cycles with ramifications for crop and soil health. Furthermore, the relationships between soil moisture and the rates of PCA biosynthesis and degradation have not been established. In this study, expression of PCA biosynthesis genes was upregulated relative to background transcription, and persistence of PCA was slightly decreased in dryland relative to irrigated wheat rhizospheres. Biofilms in dryland rhizospheres inoculated with the PCA-producing (PCA+ ) strain Pseudomonas synxantha 2-79RN10 were more robust than those in rhizospheres inoculated with an isogenic PCA-deficient (PCA- ) mutant strain. This trend was reversed in irrigated rhizospheres. In dryland PCA+ rhizospheres, the turnover of 15 N-labelled rhizobacterial biomass was slower than in the PCA- and irrigated PCA+ treatments, and incorporation of bacterial 15 N into root cell walls was observed in multiple treatments. These results indicate that PCA promotes biofilm development in dryland rhizospheres, and likely influences crop nutrition and soil health in dryland wheat fields.

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation.

Neuroendocrine homeostasis after vagus nerve stimulation in rats.

BACKGROUND: The vagus nerve is important in maintaining HPA axis and sympatho-adrenal system (SAS) homeostasis, however little is known about the effect of vagus nerve stimulation (VNS), as used therapeutically, on these functions. Accordingly, the effect of VNS on plasma indices of HPA axis (ACTH, corticosterone), and SAS (norepinephrine, epinephrine) function were evaluated in rats. METHODS: Male rats, on day-0 (D0), underwent surgeries for implantation of catheters into the right jugular vein and programmable (VNP) or non-programmable (VND) neurocybernetic devices encircling the left cervical vagus. On D7, after a blood sample, the device in VNP rats was programmed to deliver 500 µs width, 0.25 mA current pulses at 20 Hz ('on' 30s, 'off' 5 min) followed by timed blood samples during the next 90 min. In acute studies, VNS was stopped at 60 min and the rats were perfused at 90 min to evaluate neuronal Fos immunoreactivity (Fos-IR). In chronic studies, the probe remained active. In these rats, the HPA axis response to airpuff-startle stressor (D17) and anterior pituitary CRF-receptor binding (D26) were evaluated. RESULTS: During acute VNS, plasma indices of HPA axis and SAS activity, as well as Fos-IR activation pattern in brain regions known to increase after stress, were not different between VND and VNP rats. During chronic VNS, stress-induced HPA axis responses exhibited a tendency toward faster recovery to baseline in VNP rats. CONCLUSIONS: Therapeutic VNS is not a stressor and does not compromise HPA axis or SAS homeostasis. Chronic VNS may facilitate development of efficient feedback mechanisms.

Accumulation of the antibiotic phenazine-1-carboxylic acid in the rhizosphere of dryland cereals.

Natural antibiotics are thought to function in the defense, fitness, competitiveness, biocontrol activity, communication, and gene regulation of microorganisms. However, the scale and quantitative aspects of antibiotic production in natural settings are poorly understood. We addressed these fundamental questions by assessing the geographic distribution of indigenous phenazine-producing (Phz(+)) Pseudomonas spp. and the accumulation of the broad-spectrum antibiotic phenazine-1-carboxylic acid (PCA) in the rhizosphere of wheat grown in the low-precipitation zone (<350 mm) of the Columbia Plateau and in adjacent, higher-precipitation areas. Plants were collected from 61 commercial wheat fields located within an area of about 22,000 km(2). Phz(+) Pseudomonas spp. were detected in all sampled fields, with mean population sizes ranging from log 3.2 to log 7.1 g(-1) (fresh weight) of roots. Linear regression analysis demonstrated a significant inverse relationship between annual precipitation and the proportion of plants colonized by Phz(+) Pseudomonas spp. (r(2) = 0.36, P = 0.0001). PCA was detected at up to nanomolar concentrations in the rhizosphere of plants from 26 of 29 fields that were selected for antibiotic quantitation. There was a direct relationship between the amount of PCA extracted from the rhizosphere and the population density of Phz(+) pseudomonads (r(2) = 0.46, P = 0.0006). This is the first demonstration of accumulation of significant quantities of a natural antibiotic across a terrestrial ecosystem. Our results strongly suggest that natural antibiotics can transiently accumulate in the plant rhizosphere in amounts sufficient not only for inter- and intraspecies signaling but also for the direct inhibition of sensitive organisms.

Biological control of take-all by fluorescent Pseudomonas spp. from Chinese wheat fields.

Take-all disease of wheat caused by the soilborne fungus Gaeumannomyces graminis var. tritici is one of the most important root diseases of wheat worldwide. Bacteria were isolated from winter wheat from irrigated and rainfed fields in Hebei and Jiangsu provinces in China, respectively. Samples from rhizosphere soil, roots, stems, and leaves were plated onto King's medium B agar and 553 isolates were selected. On the basis of in vitro tests, 105 isolates (19% of the total) inhibited G. graminis var. tritici and all were identified as Pseudomonas spp. by amplified ribosomal DNA restriction analysis. Based on biocontrol assays, 13 strains were selected for further analysis. All of them aggressively colonized the rhizosphere of wheat and suppressed take-all. Of the 13 strains, 3 (HC9-07, HC13-07, and JC14-07, all stem endophytes) had genes for the biosynthesis of phenazine-1-carboxylic acid (PCA) but none had genes for the production of 2,4-diacetylphloroglucinol, pyoluteorin, or pyrrolnitrin. High-pressure liquid chromatography (HPLC) analysis of 2-day-old cultures confirmed that HC9-07, HC13-07, and JC14-07 produced PCA but no other phenazines were detected. HPLC quantitative time-of-flight 2 mass-spectrometry analysis of extracts from roots of spring wheat colonized by HC9-07, HC13-07, or Pseudomonas fluorescens 2-79 demonstrated that all three strains produced PCA in the rhizosphere. Loss of PCA production by strain HC9-07 resulted in a loss of biocontrol activity. Analysis of DNA sequences within the key phenazine biosynthesis gene phzF and of 16S rDNA indicated that strains HC9-07, HC13-07, and JC14-07 were similar to the well-described PCA producer P. fluorescens 2-79. This is the first report of 2-79-like bacteria being isolated from Asia.

Linkage analysis of plasma dopamine ß-hydroxylase activity in families of patients with schizophrenia.

Dopamine ß-hydroxylase (DßH) catalyzes the conversion of dopamine to norepinephrine. DßH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DßH activity (pDßH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDßH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDßH. Prior studies have suggested that variation in pDßH, or genetic variants at DßH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDßH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDßH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD = 3.1 at 27.2 cM). The present results provide the first direct evidence for linkage between DBH and pDßH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDßH, and suggest that a locus near 20p12 also influences pDßH.

Genotype-controlled analysis of serum dopamine ß-hydroxylase activity in civilian post-traumatic stress disorder.

BACKGROUND: Norepinephrine (NE) plays a central role in post-traumatic stress disorder (PTSD). Dopamine ß-hydroxylase (DßH) converts dopamine (DA) to NE and its activity varies widely across individuals. Mustapic et al. (2007) reported a PTSD-associated deficit in serum DßH activity in a genotype-controlled analysis of combat veterans. We tested whether such a deficit would occur in a sample of civilians. METHODS: The severity of current adult PTSD symptoms and current DSM-IV diagnosis of PTSD were determined by the PTSD Symptom Scale (PSS). Adulthood trauma exposure was assessed using the Traumatic Experience Inventory (TEI). Serum DßH activity (sDßH) was assayed by HPLC with electrochemical detection and genotypes were determined using the Taqman® platform. RESULTS: Two hundred and twenty seven African American (AA) subjects were enrolled in this study, with a mean age (±SD) of 42.9 (±12.9) years. We found a strong association between rs1611115 genotype and sDßH (p<0.0001). After controlling for adulthood trauma exposure, there were no significant differences of sDßH between subjects who met a PTSD diagnosis and those who did not (p>0.05) in any genotype group. No significant correlations were found between sDßH and PTSD severity, but sDßH significantly associated with the status of comorbid depression based on the cutoff of HAMD (p=0.014) in subjects with PTSD. CONCLUSIONS: We have replicated in this sample the prior finding that DBH rs1611115 genotype strongly associates with sDßH. No associations between sDßH and PTSD diagnosis or symptom severity were found in this civilian sample.

Neurohormonal and inflammatory hyper-responsiveness to acute mental stress in depression.

Depression is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis function, overactivity of the sympathoadrenal system, and increased levels of inflammation markers. It is not known whether these biological processes are disproportionately elevated in response to acute negative emotional arousal by mental stress (MS). The present study investigates responses of neurohormones and inflammatory markers to MS in 14 clinically depressed (age: 42+/-10 years; 50% female) and 14 non-depressed control (age: 39+/-6 years; 50% female) participants. Heightened acute MS reactivity was documented in depressed participants (adrenocorticotropic hormone, rho=0.001; norepinephrine, rho=0.042; epinephrine, rho=0.039), and a delayed increase in cortisol was observed (rho=0.002). Inflammation markers increased more strongly in depressed versus non-depressed participants (IL-6, rho=0.027; tumor necrosis factor-alpha, rho=0.050; and recovery C-reactive protein, rho=0.003). It is concluded that depressed individuals display hyper-reactivity of neuroimmunological markers in response to acute negative emotions. This hyper-reactivity may serve a pathologic role in the elevated morbidity and mortality risk associated with depression.

Platelet thromboxane A2 secretion in patients with major depression responsive to electroconvulsive therapy.

OBJECTIVE: To determine a) whether clinical response to electroconvulsive therapy (ECT) is associated with decreased platelet activation in patients with major depressive disorder (MDD) and b) if any medical/demographic characteristics predict response to ECT or changes in platelet activation. Increased platelet activation may underlie the increased risk of coronary artery disease (CAD) in patients with MDD. METHODS: Before their first and sixth ECT treatments, study patients (n = 44) completed the Beck Depression Inventory (BDI) to assess the severity of depressive symptoms. Activity of the platelet thromboxane (TBX) A(2) pathway was assessed by measuring the morning spot urinary concentrations of 11-dehydroxy-thromboxane B(2) (11-D-TBX B(2)), a major metabolite of platelet-derived TBX A(2). RESULTS: Multivariate logistic regression analyses revealed that improvement on the BDI was significantly more likely in patients without a history of hypertension (p = .02) and in patients who were prescribed a greater number of "platelet-altering" medications (p = .03). During a course of ECT, a decrease in urinary 11-D-TBX B(2) was significantly more likely to occur in ECT nonresponders (p = .01) and younger patients (p = .02). CONCLUSIONS: Clinical response to ECT coadministered may not be associated with decreases in platelet-derived TBX. Future studies will confirm which somatic "antidepression" treatments offer optimal thrombovascular benefits for depressed patients with multiple risk factors for, or clinically evident, cerebral disease or CAD.

Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls.

Physical and mental stressors result in increased inflammation markers in populations free of coronary artery disease (CAD). However, inflammatory responses to mental and exercise challenges have not been established in patients with CAD. This study investigated the responses of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1, in patients with CAD after successful elective percutaneous coronary intervention (n = 36, 59 +/- 8 years of age, 33% women) and healthy controls without a history of CAD (n = 28, 54 +/- 10 years of age, 36% women). Increases in inflammatory markers were examined in response to mental challenge tasks (anger recall and mental arithmetic) and treadmill exercise. Stress echocardiography was used to rule out stress-induced ischemia as a possible confounding factor. Results showed that CRP increased significantly to mental challenge and exercise (p values <0.01), and CRP responses were higher in patients with CAD than in controls (change in mental arithmetic 0.19 +/- 0.11 vs 0.01 +/- 0.03 mg/L, p = 0.003; change in exercise 0.57 +/- 0.11 vs 0.08 +/- 0.0.03 mg/L, p = 0.001). Increased norepinephrine responses were related to larger CRP and IL-6 increases to mental challenge tasks (p values <0.05). Exercise elicited increased CRP, IL-6, and soluble intercellular adhesion molecule-1 levels (p values <0.01), and these responses were larger than with mental challenge tasks (p values <0.05). In conclusion, mental stress and exercise induce increased levels of inflammatory markers in patients with CAD. These stress-induced increases are larger than in healthy subjects, occur in the absence of myocardial ischemia, and are related to the neurohormonal stress response.

Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice.

RATIONALE: Dopamine beta-hydroxylase (DBH) converts dopamine (DA) to norepinephrine (NE), thus playing a critical role in catecholamine metabolism. OBJECTIVES/METHODS: We examined the effects of Dbh gene dosage and the DBH inhibitor disulfiram in mice with zero, one, or two null Dbh alleles (+/+, +/-, and-/- mice). RESULTS: DBH protein levels in adrenal and prefrontal cortex (PFC) and adrenal DBH activity were proportional to number of wild-type alleles. Adrenal DA was slightly increased in+/- mice and markedly increased (80-fold) in -/- mice compared to wild-type animals. While adrenal NE and epinephrine (EPI) were undetectable in -/- mice, adrenal concentrations of NE and EPI were similar in +/+ and +/- mice, suggesting that the increase in DA maintains the normal rate of beta-hydroxylation in Dbh +/- mice. Disulfiram had little effect on adrenal catecholamine levels, regardless of genotype or dose. NE was absent in the PFC of -/- mice, but only slightly reduced in +/- animals compared to wild-type animals. PFC DA was increased twofold in +/- mice and fivefold in -/- mice, and the NE to DA ratio was reduced ( approximately 35%) in +/- mice, compared to wild-type mice. Disulfiram significantly decreased PFC NE and increased DA in +/+ and +/- animals, with the disulfiram and genotype effects on the PFC NE to DA ratio apparently additive. CONCLUSIONS: The data reveal potentially important and apparently additive effects of Dbh genotype and disulfiram administration on PFC catecholamine metabolism. These effects may have implications for genetic control of DBH activity in humans and for understanding therapeutic effects of disulfiram.

Pituitary-adrenal responses to standard and low-dose dexamethasone suppression tests in adult survivors of child abuse.

BACKGROUND: Previous studies indicate that adverse childhood events are associated with persistent changes in corticotropin-releasing factor neuronal systems. Our aim was to determine whether altered glucocorticoid feedback mediates the neuroendocrine sequelae of childhood trauma. METHODS: Standard and low-dose dexamethasone suppression tests (DST) were performed in women with a history of child abuse (n=19), child abuse and major depression (n=16), major depression and no childhood trauma (n=10), and no history of mental illness or childhood trauma (n=19). Secondary analysis with posttraumatic stress disorder (PTSD) as the organizing diagnosis was also conducted. RESULTS: In the low-dose DST, depressed women with a history of abuse exhibited greater cortisol suppression than any comparator group and greater corticotropin suppression than healthy volunteers or nondepressed abuse survivors. There were no differences between nondepressed abuse survivors and healthy volunteers in the low-dose DST or between any subject groups in the standard DST. The PTSD analysis produced similar results. CONCLUSIONS: Cortisol supersuppression is evident in psychiatrically ill trauma survivors, but not in nondepressed abuse survivors, indicating that enhanced glucocorticoid feedback is not an invariable consequence of childhood trauma but is more related to the resultant psychiatric illness in traumatized individuals.

Transformation of Pseudomonas fluorescens with genes for biosynthesis of phenazine-1-carboxylic acid improves biocontrol of rhizoctonia root rot and in situ antibiotic production.

A seven-gene operon for the synthesis of phenazine-1-carboxylic acid was introduced into Pseudomonas fluorescens Q8r1-96, an aggressive root colonizer that produces 2,4-diacetylphloroglucinol and consistently suppresses take-all of wheat. The recombinant strains produced both antifungal metabolites and maintained population sizes comparable to those of Q8r1-96 over a seven-week period in the rhizosphere of wheat. The strains were no more suppressive of take-all or Pythium root rot than was Q8r1-96, but suppressed Rhizoctonia root rot at a dose of only 10(2) CFU per seed, one to two orders of magnitude lower than the dose of Q8r1-96 required for comparable disease control.

Cerebrospinal fluid corticotropin-releasing factor (CRF) and vasopressin concentrations predict pituitary response in the CRF stimulation test: a multiple regression analysis.

There is considerable evidence that stress-related psychiatric disorders, including depression and post-traumatic stress disorder (PTSD), are associated with hypersecretion of corticotropin-releasing factor (CRF) within the central nervous system (CNS). One line of evidence that is consistent with central CRF hypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response to intravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The present study tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, arginine vasopressin (AVP), are associated with diminished adenohypophyseal responses in a standard CRF stimulation test. CSF concentrations of CRF and AVP, and plasma ACTH responses to the administration of 1 microg/kg ovine CRF (oCRF) were measured in healthy adult women with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure was ACTH area under the curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSF CRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression model explained 56.5% of the variation in the ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best described by a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response with CSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that central CRF hypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% of the variation in the ACTH response to CRF.

Plasma hormones and catecholamine metabolites in monozygotic twins discordant for psychosis.

OBJECTIVE: To examine plasma cortisol, adrencorticotropin hormone, and indicators of catecholamine activity in monozygotic twins discordant for schizophrenia or major affective disorders. BACKGROUND: Previous research has suggested that catecholamines play a role in the etiology of major mental illness. Several findings have also shown an inverse relation between hippocampal volume and cortisol levels in psychiatric populations including patients who are depressed and patients with Cushing disease. METHOD: In this study, plasma obtained from monozygotic twin pairs discordant for schizophrenia (n = 10) or major affective disorder (n = 3) was assayed for epinephrine, norepinephrine, dihydroxyphenylacetic acid, homovanillic acid, adrencorticotropin hormone, and cortisol. RESULTS: There was significant concordance for levels of dihydroxyphenylacetic acid and homovanillic acid, consistent with the high concordance for indicators of dopamine activity observed in healthy monozygotic pairs. There was also concordance for adrencorticotropin hormone. However, in contrast to findings on healthy monozygotic pairs, there was no relation for epinephrine, norepinephrine, or cortisol. Among patients, there was an inverse correlation between cortisol and the magnitude of the reduction in hippocampal volume, relative to that of the healthy co-twin. CONCLUSION: These findings suggest the potential role of adrenal steroids and hippocampal function in the expression of psychosis.

Some contrasting effects of surgical and "chemical" castration on the behavior of male cynomolgus monkeys (Macaca fascicularis).

In nonhuman primates, surgical castration reduces plasma testosterone levels and male sexual behavior, and testosterone replacement restores them. Chemical castration with compounds that lower plasma testosterone levels is used clinically in the treatment of certain forms of cancer and to reduce aberrant sexual behavior in male sex offenders. In the United States, medroxyprogesterone acetate (MPA) is the drug most used to help reduce serious sexual behavioral problems in men. We were therefore interested in comparing the behavioral effects of MPA treatment (40 mg once a week) in 4 intact male cynomolgus monkeys (4 pairs, 120 tests) with data from an earlier study in our laboratory on 4 males observed before and after surgical castration (16 pairs, 192 tests). Both MPA treatment and surgical castration reduced plasma testosterone to very low levels and decreased ejaculatory activity, but MPA treatment additionally affected measures of male sexual motivation (decreased numbers of male mounting attempts and increased mounting attempt latencies) which were not primarily affected by surgical astration. However, surgical castration decreased intromission ability (percentage of intromitted thrusts per test) and male yawning behavior more rapidly than did MPA treatment. This suggested a hypothesis that different mechanisms could be involved in the behavioral effects-namely, that surgical castration may act primarily via testosterone-dependent peripheral mechanisms, while chemical castration with MPA does so primarily via central mechanisms regulating sexual motivation.

A computerized system for scoring primate behavior using standard keyboards.

A scoring system has been developed for primate behavior which uses standard keyboards and minicomputers or microcomputers. The mnemonic, alphanumeric code used is easily learned, highly flexible, and can be recorded in longhand for later entry into a computer if a keyboard is not immediately available. The software consists of two programs, both of which can be written in BASIC. SCORE is used for data acquisition and appends the test time to each behavioral sequence. DATSUM decodes and summarizes the test data using table-driven logic. The minimum hardware required is a 16K microcomputer, an alphanumeric keyboard, a display, and cassette storage.