Morphological and functional variations of Leydig cells in testis of the domestic pig during the different biological stages of development.

The relationship of morphometrical and androgen receptor evaluations of the main testicular interstitium cellular element (Leydig cells) in the domestic pig provided interesting numerical and morphological features during the different aging stages. As early as 25 days (a period in which the pig is sexually immature) there was a low number of Leydig cells (1.46 x 10(8)) with respect to a 78% and 35% increase in the adult (2.48 x 108) and aged (1.78 x 10(8)) animal, respectively. Interestingly, when the volume density of Leydig cells was considered, the average volume of these cells seemed to be high (75%) in the aged pig with respect to the young immature animal whereas a lower increase (27%) was observed for the adult animal. Moreover, the evaluation of testosterone receptor binding sites in the testis at the various stages of development also displayed a differentiated pattern since elevated testosterone receptor binding levels of the high dissociation affinity type were obtained for the adult pig. Thus, from the combined morphological variations of Leydig cells and testosterone receptor binding activity, it appears that this androgenic receptor component exerts distinct autocrine effects on the different functional features of some testicular tissue constituents at the different aging stages of the domestic pig.

Dimorphic features of the different alpha-containing GABA-A receptor subtypes in the cortico-basal ganglia system of two distantly related mammals (hedgehog and rat)

This investigation represents a first study dealing with the dimorphic differences of the main alpha-containing gamma-aminobutyric acid (GABA(A)) receptors in the brain of two distantly related mammals (hedgehog and rat). The labeling of these receptors in the presence of zolpidem (highly selective benzodiazepine agonist) and under the different degree of GABA(A)/benzodiazepine allosteric coupling activities accounted for a heterogeneous colocalization of alpha1-enriched and of alpha2/3-enriched and alpha5-enriched GABA(A) receptors in some areas of the cortico-basal ganglia system (including the important ventrolateral thalamic station) of both mammalian sexes. In the hedgehog, the greatest (P<0.001) GABA-dependent reduction of zolpidem inhibition constants was mostly registered in alpha1- and/or alpha5-enriched areas, such as the frontoparietal cortex lamina III (235%), ventrolateral thalamic nucleus (128%), and substantia nigra pars reticulata (110%) of the male. However, the greatest reductions in the rat were instead detected in the male substantia nigra pars reticulata (192%) and female striatum (120%), areas which are enriched either by the colocalization of alpha1- with alpha2/3-subunits or by all three alpha-subunits. These results support the contention that a sex-related alpha-containing GABA(A) receptor sensitivity constitutes an important element in the execution of skilled motor activities during the different socio-sexual behaviors of the two mammals.

Immunoscintigraphy of atherosclerotic uncomplicated lesions in vivo with a monoclonal antibody against D-dimers of insoluble fibrin.

To test the effectiveness of a new F(ab')2 monoclonal antibody against human fragment D-dimer of cross-linked fibrin in the detection of uncomplicated atherosclerotic lesions of the carotid vessel previously documented at echo-color-Doppler and selective arteriographic study, 8 patients underwent a scintigraphic study including dynamic and early and delayed (3 h later) static imaging of the neck after injection of a bolus of 99mTc-labeled monoclonal antibody, and were subsequently operated. Vessel specimens and blood samples were drawn at operation and counted. No adverse reaction occurred after administration of the monoclonal antibody. The atherosclerotic lesion appeared as a focal area of asymmetrical tracer uptake, already visible at early images in four patients, and at delayed images in five. The average tracer uptake ratio between pathological and normal vessels was 1.40+0.24 (P < 0.05) at time-activity curves derived from dynamic images, 2.17+/-0.97 (P < 0.05) at early static images and 2.05+/-0.98 (P < 0.05) at delayed static images, respectively. Mean vessel to blood uptake rate of specimens obtained at operation was 2.22+/-0.59 (P < 0.001). The study shows that the 99mTc-labeled antibody was found to be safe and capable of detecting atherosclerotic plaques in humans.

Immunoscintigraphy of venous thrombi: clinical effectiveness of a new antifibrin D-dimer monoclonal antibody.

Safety and thrombus imaging capabilities of the 99mTc-labeled form of a new F(ab')2 monoclonal antibody (MoAb) against fragment D dimers from cross-linked human fibrin, previously shown to be effective labeled to 131I in detecting venous thrombi in the rabbit, were investigated. Sixteen patients (seven men, mean age: 60+/-7 years) with deep (n = three) and superficial (n = 13) venous thromboses of the lower limbs documented at echo-Doppler study underwent, 24 hours before saphenous vein stripping, a scintigraphic study after IV injection of the 99mTc-MoAb (1,129+/-275 MBq/mL), acquiring dynamic images, as well as early and delayed static images of lower limbs. Tracer activity was compared in normal and pathologic areas. At the operation, vessel wall including the thrombotic lesion was isolated, weighed, and counted. Blood radioactivity and MoAb concentration were also measured. No adverse reaction was observed after MoAb administration. Thrombus site appeared as a focal area (hot spot) of asymmetrically increased tracer uptake, already detectable at early images in all patients. All thrombi detected at echo-Doppler study (n=25) were confirmed at scintigraphic study, which showed four additional hot spots subsequently confirmed to represent thrombi at operation. Average percent ratio between pathologic and normal regions was 1.51+/-1.34 (p < 0.05) at time-activity curves, 2.27+/-1.1 (p < 0.05) at early static images, and 2.15+/-1.2 (p < 0.05) at delayed images, respectively. Thrombus-to-blood uptake ratio was 4.3+/-0.9 (p < 0.01). The F(ab')2 MoAb proved to be safe, and low levels of antimouse antibodies were detected in response, although further studies are needed to assess tolerance and effectiveness in case of a second administration in the same patient. The 99mTc-labeled MoAb was very effective in identifying venous thromboses both at deep and superficial localizations, although its sensitivity and specificity need be evaluated in a more numerous group, including also patients with different and clinically more relevant localizations, such as caval thromboses. However, the possibility of obtaining high-quality images within 4 hours of MoAb administration is clinically relevant, and carries also therapeutic implications, especially in pulmonary thromboembolism.

Preoperative identification of viable myocardium: effectiveness of nitroglycerine-induced changes in myocardial Sestamibi uptake.

In order to predict tissue viability in infarcted myocardial areas, changes induced by nitroglycerine infusion on Sestamibi myocardial uptake were evaluated in 37 patients with previously confirmed myocardial infarction undergoing coronary artery bypass grafting, and compared with echocardiographic and perfusional changes occurring after the operation. The improvement of Sestamibi uptake after nitroglycerine correctly classified 24/26 (92%) patients showing postoperative improvement of wall motion in the infarcted area, whereas 24/31 (77%) patients with nitroglycerine-induced increase in Sestamibi uptake had improved wall motion after operation. The presence of collateral flow to the infarcted area was associated with a significantly (P < 0.01) higher increase in Sestamibi uptake both during nitroglycerine infusion and postoperatively. An increase in wall motion score after operation was associated with a significantly higher (P < 0.05) increase in Sestamibi uptake score during nitroglycerine infusion. Thus, the results of this study suggest that Sestamibi perfusional myocardial scintigraphy during nitroglycerine infusion is capable of assessing viable but chronically hypoperfused myocardium and predicting postoperative wall motion and perfusional improvement, to yield the best results in patients with evidence of collateral circulation that supplies the infarcted area.

Acute oral trimetazidine administration increases resting technetium 99m sestamibi uptake in hibernating myocardium.

BACKGROUND: Trimetazidine is an antiischemic drug protecting the myocardium from ischemic damage through the preservation of mitochondrial oxidative metabolism, without any hemodynamic effect. 99mTc-sestamibi is accumulated by myocytes according to mitochondrial function. As mitochondrial metabolism is thought to be present in hibernating myocardium, the aim of the study was to investigate trimetazidine effects on infarcted and eventually hibernating myocardial areas by means of 99mTc-sestamibi perfusional scintigraphy, comparing them to postoperative recovery of wall motion. METHODS AND RESULTS: Twelve patients with previous myocardial infarction underwent 2 perfusion imaging tomographic studies at rest with 99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally), and subsequently underwent revascularization procedures. An echocardiographic study was carried out before and >3 months after revascularization. At polar map analysis of placebo scan, infarcted vascular territories (wall motion score index: 2.65 +/- 0.31) showed 73.7% +/- 10.4% of the territory with activity <2.5 SD from the mean of normals, for a severity (expressed as the sum of the standard deviations below average normal values in all abnormal pixels) of 833.8 +/- 345.7. Polar map analysis of the trimetazidine scan showed tracer uptake increased significantly in 11 of them, by 8.2% +/- 3.0% (p < 0.001) and by 180.3 +/- 111.0 SD (p < 0.001), respectively. Postoperative wall motion score index improved significantly in 9 of these territories (-0.9 +/- 0.4, p < 0.001). CONCLUSIONS: Trimetazidine-associated increase in 99mTc-sestamibi uptake in infarcted but viable myocardial areas is probably related to an improvement in mitochondrial oxidative metabolism that is essential to 99mTc-sestamibi retention. Additionally, coupling trimetazidine administration to 99mTc-sestamibi perfusional scintigraphy may represent a means of detecting viable myocardium.

99Tcm-sestamibi scintimammography in patients with suspicious breast lesions: comparison of SPET and planar images in the detection of primary tumours and axillary lymph node involvement.

Planar scintimammography with 99Tcm-sestamibi (99Tcm-MIBI) has been shown to be useful in diagnosing breast carcinoma. The aim of this study was to compare single photon emission tomography (SPET) and planar imaging for scintimammography with 99Tcm-MIBI in the detection of primary breast cancer and axillary lymph node involvement. Sixty-three females with mammographically suspicious lesions and 12 controls were evaluated. Dynamic images were acquired commencing immediately after the injection of the radiopharmaceutical, followed by multiple planar images in the supine and prone positions plus SPET supine imaging. A final histopathological diagnosis was achieved after surgery. A total of 66 breast lesions were considered. No focal uptake of 99Tcm-MIBI was observed in the breasts or axillas of the controls. In the patients with breast cancer, the sensitivity was 92.9% (39/42) for SPET, 71.4% (30/42) for supine and 85.7% (36/42) for prone planar imaging, respectively; the specificity was 87.5% for SPET and 91.6% for the planar scans. Metastatic axillary lymph node involvement was seen in 19 patients: the sensitivity was 84.2% (16/19) for SPET and 63.2% (12/19) for planar images; the specificity was 91.3% and 95.7% respectively. Our results confirm the high diagnostic accuracy of 99Tcm scintimammography in the diagnosis of breast cancer, and suggest that SPET is more sensitive than planar images, especially in detecting axillary lymph node involvement.

Technetium-99m sestamibi myocardial tomography based on dipyridamole echocardiography testing in hypertensive patients with chest pain.

The non-invasive diagnosis of coronary artery disease in hypertensives with chest pain is an important clinical concern because all exercise-dependent tests display limited feasibility and diagnostic accuracy; by contrast, dipyridamole echocardiography testing has been shown to have a similar feasibility and accuracy in hypertensive and normotensive subjects. The aim of this study was to evaluate the diagnostic capability of technetium-99m sestamibi tomography based on dipyridamole echocardiography testing in hypertensives with chest pain, and to compare the scintigraphic results with those of coronary angiography, exercise electrocardiography and dipyridamole echocardiography. Forty subjects with mild to moderate hypertension, chest pain and no previous myocardial infarction were submitted to 99mTc-sestamibi tomography (at rest and after high-dose dipyridamole echocardiography) and to exercise electrocardiography testing. At coronary angiography 22 patients (group A) had significant epicardial coronary artery disease (>/=70% stenosis of at least one major vessel) and 18 normal main coronary vessels (group B). Dipyridamole 99mTc-sestamibi imaging was positive in 21/22 patients of group A and in 5/18 of group B. Dipyridamole echocardiography was positive in 18/22 patients of group A and in 5/18 of group B. Exercise electrocardiography was positive in 15/22 patients of group A and in 11/18 of group B. Four out of five subjects in group B with positive results in all the tests showed a slow run-off of angiographic contrast medium, probably due to small-vessel disease. Significant epicardial coronary artery disease in hypertensives with chest pain is unlikely when dipyridamole 99mTc-sestamibi tomography is negative. When scintigraphy is positive, either epicardial coronary artery disease or a small-vessel disease condition is possible. The association of scintigraphy with dipyridamole echocardiography testing allows the assessment of contractile function and myocardial perfusion by a single pharmacological stress.

Technetium-99m sestamibi imaging in the detection of axillary lymph node involvement in patients with breast cancer.

BACKGROUND: The status of the axillary lymph nodes is the most important prognostic factor in breast cancer, and the findings of axillary node dissection remain the gold standard for the patients staging and prognosis. The aim of this study was to evaluate the usefulness of Tc-99m sestamibi scintigraphy in the detection of axillary node involvement. MATERIALS AND METHODS: Forty-nine patients (age range: 32-72 years) with breast cancer were studied. Dynamic images (1-20 minutes post-injection of the radiopharmaceutical) followed by multiple planar views and tomographic images were performed. Final diagnosis was achieved by histology after surgery. RESULTS: Metastatic axillary lymph node involvement was present in 21 patients: sensitivity was 81% (17/21) for tomographic and 61.9% (13/21) for planar images; specificity was 92.9% (26/28) and 96.4% (27/28), respectively. CONCLUSIONS: Tc-99m sestamibi imaging is a promising noninvasive method to detect axillary node metastases in patients with breast cancer, tomography appears more sensitive than planar views.

Scintimammography with technetium-99m tetrofosmin in suspected breast cancer.

BACKGROUND: Scintimammography with Tc-99m sestamibi has recently demonstrated a clinical usefulness in the evaluation of patients with breast lesions. The aim of this study was to assess the potential role of scintimammography using Tc-99m tetrofosmin in the detection of breast cancer. MATERIALS AND METHODS: Fifty-five patients (age range: 33-76 years) with suspicious breast abnormalities detected by mammography, and ten controls were examined. Dynamic images (1-20 min post-injection of the radiopharmaceutical) followed by three planar views were performed. Final diagnosis was achieved by hystology after surgery or excisional biopsy. RESULTS: A total of 59 breast lesions were considered. The sensitivity of Tc-99m tetrofosmin scintimammography for detection of primary breast cancer was 93.1% (27/29) and the specificity was 93.3% (28/30). No focal uptake was observed in both breasts of the control population. CONCLUSIONS: Tc-99m tetrofosmin scintimammography has high diagnostic accuracy in detecting breast cancer and may have a clinical role as complement to conventional mammography.

A three center study on the diagnostic accuracy of 99mTc-MIBI scintimammography.

In order to assess specificity and sensitivity of the prone scintimammography (PSM) in a large series with 99m-Tc MIBI, we performed a three-center study; 420 patients were studied; after mammography all the patients were submitted to PSM and biopsy and/or operation. PSM was considered positive if hot spot within the breast was observed. In palpable masses sensitivity was 0.98 and specificity 0.89, non palpable masses showed a sensitivity of 0.62 and a specificity of 0.91. When the cancers were stratified for T category the sensitivity was 0.28 in T1a 0.26 in the group of T1a carcinomas, 0.56 in T1b 0.95 in T1c and 0.97 T2 tumors. Physical factors such as attenuation. Compton scattering from chest, as well as biological factors have a role in breast tumor imaging. In the tumors smaller than 1 cm biological factors are probably involved too.

Single photon emission computerized tomography increases the sensitivity of indium-111-pentetreotide scintigraphy in detecting abdominal carcinoids.

Somatostatin (sms) receptors have been identified in carcinoids (c), so enabling their visualization with 111In-pentetreotide scintigraphy. The aim of this study was to evaluate if single photon emission computerized tomography (SPECT) can increase the sensitivity of sms receptor scintigraphy in the detection of abdominal c. 26 patients (pts) with a present, or previously operated, abdominal carcinoid were submitted to SPECT over the abdomen and multiple planar views after the injection of 111In-pentetreotide. Magnetic resonance imaging and computed tomography were also performed. In 19 pts abnormal sites of uptake were found by SPECT which localized 13 abdominal extrahepatic (in 11 pts) and 45 hepatic lesions (in 15 pts). No pathologic accumulation was seen in 7 pts in complete remission after surgery. Planar images visualized 7 abdominal extrahepatic (in 6 pts) and 26 liver tumor sites (in 10 pts), conventional procedures detected 5 abdominal extrahepatic (in 4 pts) and 36 hepatic lesions (in 10 pts). 111In-pentetreotide SPECT is more sensitive than planar scanning and conventional methods to detect abdominal c, and so may play a major role in the early and accurate mapping of tumour spread.

111In-pentetreotide detection of gastrinoma before and after surgery.

Eighteen patients with Zollinger-Ellison syndrome were studied with 111In-pentetreotide SPECT in order to localize gastrinoma, the tumour responsible for this pathology. NMR imaging was also carried out. Eight patients were operated. 111In-pentetreotide was reinjected 4 hours before operation and the radioactivity of the excised tumours counted. The nature of the withdrawn tissues was assessed by immunohistochemistry (chromogranina A). The scintigraphy was repeated 3-6 months after surgery. 111In pentetreotide SPECT was more sensitive than NMR. It was also absolutely specific because all the radioactive tumours excised showed positive chromogranin A staining. The radioactivity/gram counted in gastrinomas exceeded 10 fold the hepatic and biliary radioactivity and 20-100 folds the radioactivity of blood and omentum. In all the operated patients but three, the scintigraphy performed after surgery did not detect tumours. However complete eradication did not occur, because though 3-6 months after surgery the gastrinemia was significantly lower with respect to pre-surgery results it did not return to normal values in all patients but two.

Dimorphic distribution of the two main GABA(A) binding sites in cortical and limbic areas of a rodent living in natural environmental conditions.

Labeling of the two more important gamma-aminobutyric acidA (GABA(A)) supramolecular sites with [3H] muscimol (GABA(A)) and [3H] flunitrazepam (benzodiazepine) provided saturable, stable, and dimorphic binding activities in cortical and limbic regions of the wood mouse Apodemus sylvaticus. Of the cortical layers, which contained the highest [3H] muscimol binding levels, only the female lamina V supplied a greater (51%; P <0.01) receptor density than in the male. Areas of the limbic system instead proved to be the more favorable targets for differential GABA(A) binding levels. The highest (P <0.001) and higher levels were found in the oriens-pyramidalis CA1 layer of the hippocampus (65%) and in the vertical limb diagonal band-medial septal nucleus (48%), basolateral amygdala nucleus (45%), and ventromedial hypothalamic nucleus (43%), respectively, of the female. A similar pattern was obtained for [3H]flunitrazepam binding activity, especially in the presence of GABA. The highest and higher binding activities were obtained in the female central amygdala nucleus (78%) and in the ventromedial hypothalamic nucleus (52%), basolateral amygdala nucleus (48%), and oriens-pyramidalis CA1 layer of the hippocampus (47%), respectively, whereas higher levels were observed only in the male vertical limb diagonal band-medial septal nucleus (56%). Even in the cortical regions, the female exhibited higher (42%; cortex lamina V) and moderately higher (38%; cortex lamina VI) levels, with binding differences in the latter site plus in the basolateral amygdala nucleus occurring in a GABA-nondependent manner. From the saturation binding analyses it was possible to reveal that both maximal number of binding sites (Bmax) and mean dissociation constant (K(D)) modifications were responsible for receptor differences of the two GABAergic sites. These findings tend to suggest that dimorphic variations of the GABA(A) supramolecular sites, in some cortical and limbic regions, are strongly involved in sex-specific aggressive and reproductive activities of rodents living in their natural habitats.

99mTc anti-D-dimer MoAb detects venous thrombi in man.

Authors' work is based on the ability of a 99mTc labelled antibody (MoAb) against D-Dimer (D-D) to visualize thrombi in man. D-Dimer is a specific epitope created during the cross-linking process of fibrin strains. Five normal volunteers and 5 patients with leg varices were given 10 mCi of 99mTc anti-D-Dimer MoAb (research approved by our Ethical Committee). Each patient gave his informed consent. Scintigraphic images were taken at 5, 60, 180 min. No adverse reaction was observed. Two patients underwent saphenous stripping 3 hrs after injection, in the other 4 patients scintigraphic images were acquired at 6 and 8 hrs. Twelve hot spots were visualized. Of these, 5 were localized during operation with a pencil-like probe and exsected. Specific activity of exsected thrombi, saphenal walls and blood samples was measured. Thrombus to vein wall ratio of 2.2 +/- 0.6 and a thrombus to blood of 3.1 +/- 0.8 was measured. In non operated patients the best scintigraphic images were obtained between 60 and 180 min. 99mTc anti-D-Dimer MoAb is a promising agent for localization of thrombi.

SPECT improves accuracy of somatostatin receptor scintigraphy in abdominal carcinoid tumors.

UNLABELLED: Abdominal carcinoid tumors are often small and difficult to localize. Somatostatin receptors have been detected in carcinoids, thus enabling their in vivo visualization by scintigraphy with 111In pentetreotide, a radiolabeled somatostatin analog. The aim of this study was to determine the value of 111In-pentetreotide SPECT in the detection of abdominal carcinoids and to compare these results with the outcomes from planar scans and conventional imaging techniques. METHODS: Eighteen patients with a present, or previously operated, abdominal carcinoid were evaluated. Abdominal SPECT scans were acquired 4 hr postinjection of 111In-pentetreotide and multiple planar views were performed at 4, 24, and 48 hr. RESULTS: No adverse reactions were observed after radiopharmaceutical injection. In 13 of 18 patients, abnormal sites of uptake were found by SPECT, which localized 9 abdominal extrahepatic lesions (in 7 patients) and 33 hepatic lesions (in 10 patients). No pathologic accumulation was seen in the five patients considered in complete remission after surgery. Planar scans visualized 5 abdominal extrahepatic sites (in 4 patients) and 21 liver tumor sites (in 7 patients), while conventional procedures detected 3 abdominal extrahepatic lesions (in 2 patients) and 30 hepatic lesions (in 7 patients). CONCLUSION: Indium-111-pentetreotide scintigraphy is a safe and practical procedure. SPECT appears to be more sensitive than planar scintigraphy and conventional methods to detect abdominal carcinoids; it can increase the number of visualized tumor sites and that of patients with positive findings and may therefore have a role not only in the mapping of tumor spread but also in therapeutic decisions.

Effects of N omega-nitro-L-arginine methyl ester on benzodiazepine binding in some limbic areas of hyperlipidaemic rats.

Quantitative autoradiography techniques were used to evaluate the chronic effects of the potent nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on the binding pattern of [3H]flunitrazepam (benzodiazepine agonist) in some behaviorally key limbic areas of the genetic hyperlipidaemic Pittsburg Yoshida rat. Administration of this potent synthase inhibitor was capable of supplying higher and moderately higher binding levels in the basolateral amygdala nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%), respectively. When we tested for the binding changes in the presence of GABA (principal benzodiazepine modulator) we noticed that a physiological concentration (20 microM) of this inhibitory neurotransmitter was sufficient to induce notable changes in other limbic areas. In fact, lower binding values (-65%) were reported for the bed nucleus of stria terminalis whereas moderately higher values (+38%) were obtained for the radiatum-lacunosum molecular CA1 hippocampus layer. From the saturation studies, it was possible to observe that the major receptor variations provoked by the potent synthase inhibitor were not only due to changes in the total number of binding sites because there were variations, as in the case of the basolateral amygdala nucleus, that were instead due to differences in the affinity binding state. These results provide evidences of a GABAergic-nitric oxide synthase inhibitor interaction that might also be involved in the regulation of convulsive, anxiolytic, and aggressive behaviors that are modulated at the benzodiazepine site.

Sexual dimorphism of GABAA receptor levels in subcortical brain regions of a woodland rodent (Apodemus sylvaticus).

This is the first report of quantitative autoradiography results showing sex differences of GABAA receptor levels in brain regions of a wild rodent (wood mouse, Apodemus sylvaticus) living in its natural habitat. The labeling of this GABAergic site with its specific high affinity radioligand [3H] muscimol provided a heterogeneous and dimorphic binding pattern in some of the neural centers. In the female, higher (> or = 50 < or = 65%) to moderately higher (< 50%) binding levels than in the male, even after correction of the specific binding values using the calculated quenching coefficients, were observed in the substantia nigra pars reticulata and ventral lateral thalamic nucleus, brain centers that are relays of motor circuits. In the male, on the other hand, a higher level was only obtained in the caudateputamen. Relays of the stria terminalis-hypothalamic-central gray pathway such as the bed nucleus of the stria terminalis, the pontine central gray and the ventromedial hypothalamic nucleus, were among the other female brain areas with an extremely higher (> 65%) to higher and moderately higher binding activity than in the male. From the saturation analyses, it appeared that the binding differences were mainly due to Bmax variations, although closer examinations revealed that changes in the KD might have also accounted for [3H] muscimol binding differences, as shown by the high KD and Bmax values in the bed nucleus of the stria terminalis, the substantia nigra pars reticulata and the pontine central gray of the female wood mouse. These findings suggest that the dimorphic binding activity of GABAA receptors in the above brain regions might be involved in neuronal circuitry mechanisms related to sex-specific social behaviors in rodents living in their natural environmental conditions.