The cost-effectiveness of banning highly hazardous pesticides to prevent suicides due to pesticide self-ingestion across 14 countries: an economic modelling study.

BACKGROUND: Reducing suicides is a key Sustainable Development Goal target for improving global health. Highly hazardous pesticides are among the leading causes of death by suicide in low-income and middle-income countries. National bans of acutely toxic highly hazardous pesticides have led to substantial reductions in pesticide-attributable suicides across several countries. This study evaluated the cost-effectiveness of implementing national bans of highly hazardous pesticides to reduce the burden of pesticide suicides. METHODS: A Markov model was developed to examine the costs and health effects of implementing a national ban of highly hazardous pesticides to prevent suicides due to pesticide self-poisoning, compared with a null comparator. We used WHO cost-effectiveness and strategic planning (WHO-CHOICE) methods to estimate pesticide-attributable suicide rates for 100 years from 2017. Country-specific costs were obtained from the WHO-CHOICE database and denominated in 2017 international dollars (I$), discounted at a 3% annual rate, and health effects were measured in healthy life-years gained (HLYGs). We used a demographic projection model beginning with the country population in the baseline year (2017), split by 1-year age group and sex. Country-specific data on overall suicide rates were obtained for 2017 by age and sex from the Global Burden of Disease Study 2017 Data Resources. The analysis involved 14 countries spanning low-income to high-income settings, and cost-effectiveness ratios were analysed at the country-specific level and aggregated according to country income group and the proportion of suicides due to pesticides. FINDINGS: Banning highly hazardous pesticides across the 14 countries studied could result in about 28 000 (95% uncertainty interval [UI] 24 000-32 000) fewer suicide deaths each year at an annual cost of I$0·007 per capita (95% UI 0·006-0·008). In the population-standardised results for the base case analysis, national bans produced cost-effectiveness ratios of $94 per HLYG (95% UI 73-123) across low-income and lower-middle-income countries and $237 per HLYG (95% UI 191-303) across upper-middle-income and high-income countries. Bans were more cost-effective in countries where a high proportion of suicides are attributable to pesticide self-poisoning, reaching a cost-effectiveness ratio of $75 per HLYG (95% UI 58-99) in two countries with proportions of more than 30%. INTERPRETATION: National bans of highly hazardous pesticides are a potentially cost-effective and affordable intervention for reducing suicide deaths in countries with a high burden of suicides attributable to pesticides. However, our study findings are limited by imperfect data and assumptions that could be improved upon by future studies. FUNDING: WHO.

MUC1 is upregulated in advanced prostate cancer and is an independent prognostic factor.

BACKGROUND: MUC1 is a membrane-bound glycoprotein that belongs to the mucin family. It is involved in cell adhesion and intracellular signaling. Aberrant expression of MUC1 has been observed in different carcinomas, including prostate cancer, where it may serve as a therapeutic target. There are no data on the prognostic value of MUC1 in metastatic prostate cancer. METHODS: MUC1 expression was evaluated in tissue microarrays constructed from 119 nodal positive prostate cancer patients treated by radical prostatectomy and extended lymphadenectomy. MUC1 status was correlated with various tumor features and biochemical recurrence-free (bRFS), disease-specific survival (DSS) and overall survival (OS). RESULTS: MUC1 expression was significantly different between primary tumors, lymph node metastases and non-neoplastic glands (scores 53.7 vs 30.1 vs 16.6; P<0.0001). High MUC1 expression in primary tumors was positively correlated with tumor volume (mean 24.4 cm(3) vs 14.5 cm(3); P=0.005) and T-stage (P=0.009); in lymph node metastases, high expression corresponded with a greater total size of metastases (mean 35.8 mm vs 12.7 mm; P<0.001) and a higher ratio of positive to examined lymph nodes (mean 0.22 vs 0.12; P=0.014). High MUC1 expression in lymph node metastases predicted unfavorable outcomes compared with low MUC1 expression (bRFS P=0.023, DSS and OS P⩽0.001), whereas in primary tumors, the same tendency was non-significant. In multivariate analyses, high MUC1 expression in primary tumors and lymph node metastases independently predicted early biochemical failure (P=0.046) and tumor-related death (P=0.0038), respectively. CONCLUSIONS: High MUC1 in either primary tumor or lymph node metastases correlates significantly with unfavorable tumor features and survival. Overexpression of MUC1 in the metastases of a subset of prostate cancer patients may have therapeutic potential.

Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer.

Several (pre-) clinical trials are currently investigating the benefit of HER2-targeted therapy in urothelial bladder cancer (UBC). Patients with HER2 amplified UBC could potentially profit from these therapies. However, little is known about histomorphology, HER2 protein expression patterns and occurrence of alterations in the HER2 gene in their tumors. Among 150 metastasizing primary UBC, 13 HER2 amplified tumors were identified. Their histopathological features were compared with 13 matched, non-amplified UBC. HER2 protein expression was determined by immunohistochemistry. The 26 tumors were screened for mutations in exons 19 and 20 of the HER2 gene. UBC with HER2 amplification presented with a broad variety of histological variants (median 2 vs. 1), frequently featured micropapillary tumor components (77 % vs. 8 %) and demonstrated a high amount of tumor associated inflammation. Immunohistochemically, 10 of 13 (77 %) HER2 amplified tumors were strongly HER2 protein positive. Three tumors (23 %) were scored as HER2 negative. One of the HER2 amplified tumors harbored a D769N mutation in exon 19 of the HER2 gene; all other tested tumors were wild type. In conclusion, HER2 amplified UBC feature specific morphological characteristics. They frequently express the HER2 protein diffusely and are, therefore, promising candidates for HER2 targeted therapies. The detection of mutations at the HER2 locus might add new aspects to molecular testing of UBC.

Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene.

BACKGROUND: Overexpression of anti-apoptotic Bcl-2 plays a role in prostate cancer progression, particularly in transformation to androgen-independent disease. Androgen-independent prostate cancers have been shown to harbor Bcl-2 gene copy number gains frequently suggesting that this genetic alteration might play a role in Bcl-2 overexpression. The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown. METHODS: Prostate cancers of 3,261 hormone-naïve patients undergoing radical prostatectomy were arrayed in a TMA with one tissue core (diameter 0.6 mm) per tumor. Bcl-2 immunohistochemistry, analyzed for Bcl-2 expression level (negative, low, and high), was correlated with clinical, histopathological and molecular (Ki67, p53) tumor features, and biochemical failure. Cancers with high-level Bcl-2 expression were evaluated for genetic aberrations by fluorescence in situ hybridization (FISH). RESULTS: Bcl-2 expression was significantly up-regulated in tumors with aggressive phenotype as indicated by high Gleason score (P < 0.0001), advanced stage (P < 0.0001), and high proliferation index (P = 0.0114). The different Bcl-2 expression levels translated into significantly different survival curves showing better outcome for patients with lower Bcl-2 levels. The prognostic information obtained from the anti-apoptotic Bcl-2 was independent from the proliferation index (Ki67) of the cancer. FISH analysis detected no copy number gains or translocation of the Bcl-2 gene. CONCLUSION: Bcl-2 overexpression in prostate cancers under hormone-naïve conditions is not associated with increased copy numbers of the gene. This suggests that these frequently detected genetic alterations in androgen-independent tumors occur late in prostate cancer progression.

Benign cystic lesions in the testis of children.

Cystic lesions in the testis of children are rare and in most cases benign tumors. However, a preoperative diagnostic work-up could contribute to planning the surgical procedure: orchiectomy in the case of potential malignancy or otherwise a testis-sparing approach. In this study we reviewed our recent cases of benign cystic testicular tumors and the corresponding literature. The different entities are presented with details of the diagnostic work-up, pathology and treatment of these lesions. In all presented cases, organ-preserving treatment was performed. This practice is to be recommended in the case of all prepubertal cystic testicular lesions.

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival.

AIMS: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node-positive, hormone treatment-naive patients undergoing radical prostatectomy and extended lymphadenectomy. METHODS AND RESULTS: The median number of nodes examined per patient was 21 (range 9-68), and the median follow-up time was 92 months (range 12-191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence-free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. CONCLUSIONS: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient.

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

[The impact of methodology on the reported prevalence of thyroid pathology: comparison of two autopsy series from Switzerland performed with different methods]. / Der Einfluss der Untersuchungsmethode auf die festgestellte Prävalenz pathologischer Schilddrüsenbefunde in zwei konsekutiven Autopsieserien aus der Schweiz.

To investigate the impact of methodology on the detection and hence reported prevalence of pathological findings in thyroids, in the geographic area of Kt. Thurgau in Switzerland, we used two different methods in two consecutive autopsy series of 420 patients. In series A, the thyroids were sliced unfixed and only suspect lesions were examined histologically. In series B, the thyroids were fixed in formalin and sectioned in a standardized manner. At least one specimen per lobe was taken for histological examination. Series A revealed that five patients had adenomas, four malignant primary tumors, two metastases and four inflammatory changes in the thyroid. Series B detected ten patients with adenomas, eight with primary malignant tumors, eleven with metastases and twenty-eight with inflammatory changes in the thyroid. These differences were significant (p < 0.001). In conclusion, the methodology has an important impact on the detected prevalence of pathological findings in the thyroid.

Spontaneous dissection of common iliac artery. A case report.

Spontaneous dissection of the iliac artery is very rare but known as a complication of high-energy traumatic injuries and has been reported in connection with pregnancy, collagen diseases, and alpha-1-antitrypsin deficiency. The authors report a 42-year-old man with an acute dissection of the common iliac artery during exercise. Groin pain and claudication were the early symptoms. Computerized angiotomography was diagnostic. Operative iliac artery reconstruction was performed. A prerelease control computed tomography examination showed a dissection of the distal aorta and left iliac artery. To their knowledge, the combination of the 2 dissections has not been previously published.

Umbilical endometriosis.

We report two women who presented with a recurrent, mildly painful, bluish nodule in the umbilicus. Both patients complained of local tenderness and occasional bleeding that increased during menstruation. Neither patient had had previous pelvic surgery. Excision of the lesions revealed a primary umbilical endometriosis; in one case, a simultaneous laparoscopy showed a pelvic endometriosis. We review the current literature and discuss the possible etiopathogenesis and when a laparoscopy is indicated to diagnose a concomitant pelvic endometriosis. Umbilical endometriosis is a very rare disease but should be considered in the differential diagnosis of umbilical lesions.

[Rare seminoma metastasis to the corpus spongiosum and urethra]. / Seltene Seminommetastase im Corpus spongiosum und der Urethra.

Anaplastic seminomas account for 5-10% of all seminomas. Their metastatic pattern is similar to the classic form of seminoma. We report on an oligophrenic patient with seminoma pT1 who developed a metastasis to the corpus spongiosum and penile urethra, which was successfully treated by local external radiotherapy resulting in long-term tumor remission over a 4-year follow-up period.

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy.

PURPOSE: We evaluate the outcome in patients with node positive bladder cancer with particular reference to the effect of individual characteristics of positive nodes on survival after meticulous pelvic lymphadenectomy at cystectomy. MATERIALS AND METHODS: This prospective analysis contains 452 cases of bladder cancer staged preoperatively as N0M0, managed with pelvic lymphadenectomy and cystectomy between 1984 and 1997. A total of 83 (18%) patients with histologically confirmed node positive disease are included in our study. RESULTS: The median overall survival of patients with positive nodes was 20 months. Median 5-year survival was 29%. Patients who survived were found with positive nodes at each site in the pelvis. The median survival of 57 patients with less than 5 positive nodes was 27 months, compared with 15 months for 26 with 5 nodes or more (log-rank test p = 0.0027). Median survival of 26 patients with no lymph node capsule perforation was 93 months, compared with 16 months for 57 with capsule perforation (p = 0.0004). The median survival of 18 patients with a maximum diameter of lymph node metastasis up to 0.5 cm. was 64 months, compared with 16 months for 65 with nodal metastasis greater than 0.5 cm. (p = 0.024). Contralateral positive nodes were found in 16 of 39 (41%) patients with unilateral bladder cancer. CONCLUSIONS: Long-term survival is possible with node positive bladder cancer. Those patients with few as well as smaller and, therefore, unsuspected nodal metastases, and those without lymph node capsule perforation have the best results after removal of pelvic metastatic nodal disease. Because patients who survive may be found regardless of the site of pelvic nodal metastases, meticulous bilateral pelvic lymphadenectomy is warranted in all patients at the time of attempted curative cystectomy for bladder cancer, particularly if there is no clinical evidence of nodal involvement.

Fra-1 replaces c-Fos-dependent functions in mice.

Structure-function analysis as well as studies with knock-out and transgenic mice have assigned distinct functions to c-Fos and Fra-1, two components of the transcription factor AP-1 (activator protein-1). To test whether Fra-1 could substitute for c-Fos, we generated knock-in mice that express Fra-1 in place of c-Fos. Fra-1 rescues c-Fos-dependent functions such as bone development and light-induced photoreceptor apoptosis. Importantly, rescue of bone cell differentiation, but not photoreceptor apoptosis, is gene-dosage dependent. Moreover, Fra-1 fails to substitute for c-Fos in inducing expression of target genes in fibroblasts. These results show that c-Fos and Fra-1 have maintained functional equivalence during vertebrate evolution.

The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development.

The EGF receptor (EGFR) is required for skin development and is implicated in epithelial tumor formation. Transgenic mice expressing a dominant form of Son of Sevenless (SOS-F) in basal keratinocytes develop skin papillomas with 100% penetrance. However, tumor formation is inhibited in a hypomorphic (wa2) and null EGFR background. Similarly, EGFR-deficient fibroblasts are resistant to transformation by SOS-F and rasV12, however, tumorigenicity is restored by expression of the anti-apoptotic bcl-2 gene. The K5-SOS-F papillomas and primary keratinocytesfrom wa2 mice display increased apoptosis, reduced Akt phosphorylation and grafting experiments imply a cell-autonomous requirement for EGFR in keratinocytes. Therefore, EGFR functions as a survival factor in oncogenic transformation and provides a valuable target for therapeutic intervention in a broader range of tumors than anticipated.

Bombesin receptors in distinct tissue compartments of human pancreatic diseases.

Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest. Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n = 23) and ductal pancreatic carcinoma (n = 29) with in vitro receptor autoradiography on tissue sections incubated with 125I-[Tyr4]-bombesin or the universal ligand 125I-[D-Tyr6, beta-Ala11, Phe13, Nle14]-bombesin(6-14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in chronic pancreatitis and in peritumoral vessels around ductal pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of bombesin analogs, including GRP receptor scintigraphy to differentiate chronic pancreatitis from ductal pancreatic carcinoma.

[A normal thyroid gland upon autopsy: a relatively uncommon finding]. / Die autoptisch normale Schilddrüse: ein relativ seltener Befund.

In a series of 420 autopsies the thyroid glands have been weighed, serial sections made and examined histologically with at least one specimen per lobe. There is an age-dependent increase in mean thyroid weight. In the 7th decade the mean weight exceeds 29 g and weights above this are regarded as goitre. Between the 4th and 8th decade the incidence of goitre is 20-30%, after which the incidence rises steadily to 64% in the 10th decade. The commonest thyroid pathology is hyperplastic nodules, which are found in 39% of patients (49.4% of males and 33.4% of females). 2.4% of all patients have adenomas, 1.9% primary carcinomas and 2.8% thyroid metastases. Inflammatory infiltrates are observed in 6.6% of cases (9.4% of females and 4.4 of males). To establish the incidence of normal thyroid glands we have studied 840 serial autopsies. Only 25% of thyroids are normal (19% of females and 30% of males). The incidence of normal thyroid glands tends to decrease with age and in no decade does it reach 50%.

GABAA receptor activation induces GABA and glutamate release from preoptic area.

The effect of GABA receptor agonists on release in vitro of radiolabeled GABA and glutamate was studied using a crude preparation of isolated nerve terminals (neurosomes). GABA agonists were incubated (2 min, 37 degrees C) with neurosomes prepared from hypothalamus, preoptic area (POA) and frontal cortex tissues. Under these conditions, GABA and the GABAA receptor agonist muscimol, but not the GABAB receptor agonist baclofen, stimulated 3H-GABA and 3H-glutamate release from POA but not hypothalamic or cortical neurosomes of gonadally intact male rats. These effects were inhibited by the GABAA receptor antagonists picrotoxin, bicuculline and SR-95531. Significant efflux of 3H-glutamate could be elicited from cortical neurosomes following longer (5 min) incubations with 500 microM GABA and 400 microM muscimol. Muscimol-induced release of 3H-glutamate and 3H-GABA was dependent on extracellular calcium. Muscimol and GABA failed to release 3H-GABA or 3H-glutamate from POA neurosomes of ovariectomized female rats. However, administration of estradiol and progesterone to ovariectomized females prior to sacrifice caused the appearance of muscimol induced-release of amino acids from POA neurosomes comparable to that obtained in male rats. GABA-induced release of 3H-glutamate was similarly dependent on pretreatment of ovariectomized rats with ovarian steroids. GABAA receptor-induced release of amino acids is therefore brain region-specific and modified by hormonal status.

Characterization of glutamate efflux from preoptic area synaptosomes.

Treatment of ovariectomized rats in vivo with ovarian steroids has been found to influence the efflux of glutamate and gamma-aminobutyric acid from preoptic area synaptosomes incubated in vitro. Since these studies indicated a possible role of the glutamate carrier in steroid-modulated release of amino acids, the present studies examined the characteristics of efflux of glutamate and of the carrier system for glutamate in synaptosomes of the preoptic area derived from ovariectomized hormone-treated rats. The efflux of [3H]glutamate from preoptic area synaptosomes, was induced by glutamate and by the glutamate carrier agonist, D-aspartate; the putative glutamate carrier antagonist dihydrokainate failed to block this efflux. Dihydrokainate inhibited the uptake of glutamate but it was less effective than D-aspartate. The excitatory amino acid receptor agonists, N-methyl-D-aspartate and kainate were without effect while quisqualate modestly stimulated the efflux of [3H]glutamate. Efflux of [3H]glutamate, induced by glutamate itself or by D-aspartate was not blocked by the excitatory amino acid receptor antagonists, D-2-amino-5-phosphonovaleric acid, 6,7-dinitroquinoxaline-2,3-dione or kynurenate. Glutamate-induced efflux of [3H]glutamate did not require external Ca2+. Glutamate altered neither the basal nor the potassium-induced increases in the intrasynaptosomal concentration of Ca2+ as measured by the fura-2 method. Glutamate-induced efflux of [3H]glutamate was blocked by the putative chloride channel antagonist, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. It is concluded that the glutamate-induced efflux of [3H]glutamate in synaptosomes of the preoptic area is a carrier-mediated process that does not require activation of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol plus progesterone promote glutamate-induced release of gamma-aminobutyric acid from preoptic area synaptosomes.

Treatment of ovariectomized rats with both estradiol and progesterone in vivo resulted in a marked enhancement of glutamate-induced release of newly synthesized [3H]gamma-aminobutyric acid (GABA) from synaptosomes of the preoptic area in vitro. With this treatment, as little as 0.01 nM glutamate, in vitro, enhanced release of GABA. In contrast, glutamate, in vitro, did not stimulate release of GABA from synaptosomes, obtained from rats treated with either estradiol or progesterone alone and only large concentrations of glutamate (1.0 and 10 mM) caused a modest release of GABA from synaptosomes from ovariectomized, vehicle-treated rats. Also, treatment with estradiol plus progesterone did not alter glutamate-induced release or exchange of [3H]glutamate. Glutamate-induced release of GABA was calcium-independent and attenuated by the putative chloride channel antagonist, 4,4'-diisothiocyanatostilbene-2,2'-DL-disulfonic acid. Thus, glutamate-induced, steroid-enhanced release of GABA may occur through a chloride-dependent carrier rather than by exocytosis. In addition to enhancement by glutamate, release of GABA was also enhanced by D-aspartate, an agent that is transported by the neuronal glutamate carrier. It is postulated that enhancement of glutamate-induced release of GABA, by estradiol plus progesterone in the preoptic area, represents one process by which these steroids modulate reproductive function in female rats.

Effects of non-competitive NMDA receptor antagonists on reproductive and motor behaviors in female rats.

MK-801 and dextrorphan, selective non-competitive antagonists at N-methyl-D-aspartate (NMDA) receptors, were used to evaluate the effect of NMDA receptor blockade on sexual and motor behaviors in female rats. Ovariectomized rats were treated with estradiol benzoate (EB) for 48 or 72 h followed by progesterone (P) 3.5-4 h before testing the animals for sexual receptivity. After testing for estrous responsiveness, the effect of NMDA antagonists on several motor behaviors was also assessed. Lordosis frequency and intensity were inhibited in animals that received 0.5 mg/kg MK-801 30 min before EB; the same dose of MK-801 was relatively ineffective when administered 24 h after EB. In neither case did MK-801-treated females differ from controls when motor behaviors were assessed after mating tests. When 30 mg/kg dextrorphan, a short-acting NMDA antagonist, was administered 15 min before P, sexual behavior was not blocked. However, both 0.05 mg/kg MK-801 and 30 mg/kg dextrorphan suppressed ongoing female sexual behavior within 30 min in animals made receptive with EB and P. These deficits in sexual behavior were associated with changes in motor performance. MK-801 (0.1 mg/kg) and dextrorphan (30 mg/kg) abolished movement in the vertical dimension (e.g. jumping and rearing). By contrast, the drugs increased movement in the longitudinal (locomotion) and lateral (circling) dimensions. At 0.2 mg/kg, MK-801 blocked movement in both the vertical and longitudinal dimensions; however, it failed to block circling. Only at 0.4 mg/kg did MK-801 inhibit lateral movements and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)