ACE inhibitors and angiotensin receptor blockers could promote the onset of endometrial polyps in hypertensive women.

OBJECTIVE: To investigate whether anti-hypertensive therapy is a risk factor for the onset of endometrial polyps in hypertensive women. METHODS: A sample of 305 hypertensive patients was analyzed. By applying multivariable logistic regression analysis, the odds of developing endometrial polyps relative to the known risk factors for endometrial polyps and to the class of anti-hypertensive drugs were calculated. RESULTS: The variables reaching significance after multivariable logistic regression analysis included the following: hypertension not-in-therapy (odds ratio 2.544; 95% confidence intervals 1.249 - 5.182; p = 0.010); ACE inhibitor therapy (odds ratio 2.400; 95% confidence intervals 1.248 - 4.614; p = 0.009); angiotensin receptor blockers (odds ratio 2.091; 95% confidence intervals 1.044 - 4.187; p = 0.037); and fasting glucose level (odds ratio 1.018; 95% confidence intervals 1.007 - 1.030; p = 0.001). CONCLUSIONS: Although the results should be interpreted carefully, it appears that ACE inhibitors and, to a lesser extent, angiotensin receptor blockers may promote the onset of endometrial polyps in hypertensive patients.

RETRACTION: Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus.

On behalf of the coauthors and with much regret, I must retract our publication entitled "Intrinsic innervation and dopaminergic markers after experimental denervation in rat thymus" published in European Journal of Histochemistry 2010;54(2):e17 for the following reason: Unfortunately, now, after thirteen years, we have realized that some microphotographs published in the paper have been processed to improve the presentation of the images. The three surviving authors of the paper agree that the processing of the presentation images is against the COPE Ethical Editorial Standard, although the presentation images do not alter the integrity of methodological procedures and the results of the research work, obtained from the direct analysis of slides under microscope and rigorous statistical analysis of data; therefore, we, the authors of the above indicated paper, request the retraction of the publication. We apologize for what happened.   Maurizio Sabbatini Dip. di Scienze e Innovazione Tecnologica (DISIT) Università del Piemonte Orientale Alessandria, Italy.

Neuropeptide expression and T-lymphocyte recruitment in facial nucleus after facial nerve axotomy.

Axonal injury in the peripheral nervous system can have a strong impact on the neurons and the surrounding non-neuronals cells. The aim of this study was to evaluate the immunohistochemistry signals of the vasoactive intestinal peptide (VIP), substance P (SP), and CD3+ T cells and the messenger RNA levels of neuropeptides in the facial nucleus (FN) at 7, 14, and 21 days after peripheral facial nerve axotomy. Moreover, the authors assayed the peripheral blood levels of interleukin (IL-1ß), tumor necrosis factor-α, and IL-6 serum levels at 24 and 48 hours after the surgical procedures. Immunohistochemistry analysis revealed that VIP and SP expression is strongly induced in FN after peripheral facial nerve axotomy at 7 days, the CD3+ pan-T cells peak at 14 days. Polymerase chain reaction analysis for VIP and SP messenger RNA levels confirms the immunohistochemical data, but VIP level remains significantly high for 14 days. The serum level of IL-6 48 hours after axotomy was significantly higher than after 24 hours; there were no significant changes for IL-1ß and tumor necrosis factor-α serum levels between 24 and 48 hours. Our data reveal that FN neurons are under neuropeptidergic influence and show that modulation/modification of VIP and SP expression in FN injury models facilitates the crossing of the blood-brain barrier. On the contrary, our results emphasize the role of the T cells in preventing initial neurodegeneration or neuronal death. The high serum levels of IL-6 at 1 to 2 days suggest that this cytokine could play a central role in the initiation of immunosurveillance and provide advance information on the recruitment of CD3+ T lymphocytes in the FN.

Age- and gender-specific epistasis between ADA and TNF-α influences human life-expectancy.

Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-α) genes may influence human life-expectancy. ADA (22G>A, rs73598374) and TNF-α (-308G>A, rs1800629; -238G>A, rs361525) functional SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals<66 years old (<73 years old), the second class of individuals 66-88 years old (73-91 years old), and the third class of individuals>88 years old (>91 years old). Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males (comparison 1 (age class 2 vs. age class 1), O.R. 1.943, P=0.036; comparison 2 (age class 3 vs. age class 2), O.R. 0.320, P=0.0056). Age- and gender-specific patterns of epistasis between ADA and TNF-α were found using Generalized Multifactor Dimensionality Reduction (GMDR). In comparison 1, a significant two-loci interaction occurs in females between ADA 22G>A and TNF-α -238G>A (Sign Test P=0.011). In comparison 2, both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88 years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-α genes can influence life-expectancy in a gender-specific manner and that males and females follow different pathways to attain longevity.

Dopamine receptor subtypes in the native human heart.

The present study first time detected D1-D5 dopamine receptor subtypes in the native human heart simultaneously, found presence of D1, D2, D4, and D5 in cardiac tissues, and revealed distribution features of dopamine receptor subtypes in the epicardium, myocardium, and endocardium. Samples from four native hearts coming from young brain-dead donors, which for technical reason were not used for transplants, were studied. Dopamine receptors were revealed by immunochemistry technique and immunoblot analysis. Morphometrical quantification of the density of each receptor subtype was performed by an image analyzer. Our results demonstrate that only four subtypes of dopamine receptors can be found in cardiac tissues: D1, D2, D4, and D5. These dopamine receptors have been detected in endocardium, myocardium, and epicardium. D1 receptors were stored primarily in the epicardial layer. Dopamine receptors are distributed in the wall of both atria and ventricles, and its transmural gradient can be described in the wall of the human heart. Sections of atria and ventricles exposed to antidopamine receptor antibodies showed fluorescent-positive reaction in the epicardium, myocardium and endocardium. D4 receptor immune reactivity was remarkably less intense than D2 receptor immune reactivity. All the subtypes of dopamine receptors are in close relationships with all cardiac structures. Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases.

Dopamine, vesicular transporters and dopamine receptor expression and localization in rat thymus and spleen.

The localization of dopamine stores and the expression and localization of vesicular monoamine transporter (VMAT) type-1 and 2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat thymus and spleen by immunohistochemical, immunochemical techniques and by RT-PCR. In the thymus dopamine immunoreactivity was developed in the cortico-medullary junction and in the medulla, but not in the thymic cortex. In the spleen, dopamine stores were found in reticular structures in the white pulp border and in the white pulp, but not in the red one. Both thymus and spleen expressed VMAT-1 and VMAT-2 immunoreactivity as well as dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity. Immunohistochemistry revealed VMAT-1, VMAT-2 and dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity primarily in the thymic cortical-medulla transitional zone and to a lesser extent in the medulla but not in the cortex. In the spleen, VMAT-1, VMAT-2 and dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity was located primarily in the white pulp border and to a lesser extent in the white pulp. These findings indicate that both thymus and spleen express a dopaminergic system characterized by the presence of dopamine, vesicular monoamine transporters and the five subtypes of dopamine receptors. The presence of these dopaminergic markers suggests that dopamine likely originating from immune cells and/or from sympathetic neuroeffector plexus is released in the lymphoid microenvironment. Based on the microanatomical localization of dopaminergic markers investigated, a role of dopamine in maturation and selection of lymphocytes and activation of immune responses is suggested.

Immunological pattern alteration in shoe, hide, and leather industry workers exposed to hexavalent chromium.

OBJECTIVE: The aim of this work was to assess the effects of hexavalent chromium [Cr(VI)] on shoe, leather, and hide industry workers, based on the assumption that Cr(VI) can behave as an environmental immunological "stressor." METHODS: The immunological patterns of 84 male subjects were studied in relation to Cr(VI) hematic and urinary levels. Cr(VI) was measured through atomic absorption. Lymphocyte subsets, mitogen-mediated lymphocyte-proliferation, cytokine levels, and natural killer (NK) cytotoxic activity were also assayed. RESULTS: The urinary levels of the total amount of Cr(VI) were significantly higher in a subgroup of exposed subjects (group B) than in the control or in the lower exposed (group A). In group B, Cr(VI) caused a decrease in the density of glucocorticoid receptors (GR) on peripheral blood mononuclear cells (PBMC) and a increase of IL-6. Cr(VI) did not modify NK-mediated cytotoxicity, the plasmatic levels of inflammatory cytokines and related soluble receptors, and prostaglandin levels, while it tended to increase lymphocyte sensitivity to mitogens and the production of immunomodulant cytokines (IFN-gamma, IL-4, and IL-2). The experimental addition of Cr(VI) to the in vitro lymphocyte culture determined a significant inhibition of phagocytosis percentage, index, and killing percentage. These effects were neutralized by exogenous IFN-gamma. CONCLUSION: Cr(VI) could represent an environmental immunological stressor whose effects can be evaluated through laboratory surveys. The lymphocyte mitogen-induced proliferation, GR receptor on PBMC, and IL-6 plasma levels may represent a discriminating element between Cr(VI)-induced stress and other kinds of stress.

Antioxidant endogenous defense in a human model of physical stress.

The present work has used controlled conditions to study how physical activity and stress affect oxidant and anti-oxidant systems in a human model. Stress test consisting of one hour exercise at a cycloergometer with intensity over the 75% of the maximal cardiac frequency was followed by non-significant changes of malonyldialdehyde, assayed as a marker of lipid peroxidation, and by an increase of erythrocyte catalase and plasma and erythrocyte glutathione peroxidase after the test. These findings suggest that antioxidant response is broadly versatile and adaptable, and that physical activity may prevent extended cellular damage with consequent flogosis. Hence, controlled physical exercise may contribute to protect target organs, including cardiovascular systems, against oxidative stress.

Pharmacokinetics of different formulations of tioctic (alpha-lipoic) acid in healthy volunteers.

This study was designed to evaluate in healthy volunteers plasma and cellular (in erythrocytes) of three formulations of alpha-lipoic acid (ALA) available in Italy with different rates of absorption, two with a claimed high absorption rate (Byodinoral 600 QR, Tiocronal 600 HR) and one with a claimed prolonged absorption rate (Tiobec 600 retard). These formulations were compared with the registered ethic formulation of the compound (Thioctacid 600 mg HR), available in Germany. Area under the curve from time 0 to last measured time (AUC(t)), peak plasma concentration (C(max)) of ALA, and time (T(max) ) at which C(max) was observed were the plasma kinetic parameters measured. Concentration of ALA at different sampling times was the only parameter assessed for erythrocytes. The AUC(t) values were similar for the four formulations of ALA tested. C(max) was significantly higher for Byodinoral 600 QR, Tiocronal 600 HR compared to Thioctacid 600 mg HR or Tiobec 600 retard, whereas T(max) value was significantly shorter for Byodinoral 600 QR in the order by Tiocronal 600 HR, Thioctacid 600 mg HR, and Tiobec 600 retard. ALA concentrations that accumulated in erytrocytes after the administration of the different formulations of the antioxidant are directly proportional to the plasma levels of each formulation. Because antioxidant capabilities of ALA depend on the glutathione regeneration the compound induces in cells, the most rationale approach for eliciting antioxidant activity at the cellular level is probably in the use of a formulation allowing the compound to reach its target at highest concentrations and in the shortest time.

Leucocyte subset redistribution in a human model of physical stress.

This study has investigated, under controlled conditions, peripheral mononuclear cells (PMNC) subset redistribution in a human experimental stress model consisting of cycloergometer activity in healthy male volunteers exposed to a stressful stimulus. After stressful stimuli, leucocyte subpopulations undergo a stereotyped redistribution peculiar for each PMNC cytotype. PMNC subpopulations involved to a greater extent were natural killer (NK) cells and lymphocytes T "memory" cells. The post-stress period was characterized by a decrease of the NK subpopulation. Our findings confirm the view of a sensible functional reduction of immunocompetence in stress conditions. This brings to the opening, even if for a short time, an "immunological window." This window remains open throughout the time of the stimulus, probably representing the basis of the progressive reduction of the competency of immune system. Catecholamines support the acute effects of stress influencing the anatomical redistribution of lymphocyte subpopulation and intermediating acute effects on PMNC. Cortisol, acting for longer time, contributes to create and maintain both the neutrocytosis and lymphopenia in the post-stress period following lymphocytosis.

Nicardipine: a hypotensive dihydropyridine-type calcium antagonist with a peculiar cerebrovascular profile.

Control of blood pressure protects against the development of cerebrovascular lesions, stroke, and vascular dementia (VaD). Cerebrovascular disease is increasingly recognized as a cause of cognitive impairment and dementia primarily in the elderly. Nicardipine is a dihydropyridine-type calcium channel blocker (CCB) with a peculiar cerebrovascular profile developed approximately 30 years ago. This study has reviewed the main controlled clinical studies investigating the use of nicardipine in pathologies associated with cerebrovascular injury, such as subarachnoid haemorrhage (SAH), acute stroke, and VaD. SAH is a main cerebrovascular indication of CCBs. In this indication, CCBs prevent vasospasm and improve clinical outcomes. Nimodipine represents the CCB more investigated in this indication. Former studies did not demonstrate a clear advantage of nicardipine versus nimodipine in SAH. A more recent approach using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits, and improved clinical outcome after severe SAH. Controlled trials have shown the effectiveness of the drug in preventing stroke. Increasing evidence suggests some benefit of some CCBs in VaD or mixed degenerative and vascular dementia. In this setting, nicardipine has been investigated in approximately 6,000 patients, with an improvement of cognitive deterioration in more than 60% of patients treated. The pronounced anti-hypertensive activity of nicardipine and its safety and effectiveness in cognitive domain suggest its reconsideration in the treatment of cognitive impairment of vascular origin as well as for reducing the risk of recurrent stroke in patients at high risk of it.

Pharmacokinetics and bioequivalence study of two tablet formulations of lovastatin in healthy volunteers.

Lovastatin is a lipid-lowering agent indicated for primary hypercholesterolemia. This study has assessed single-dosing pharmacokinetics of lovastatin and of its main metabolite, lovastatin beta-hydroxyacid, and has compared the pharmacokinetics of two formulations of lovastatin, a test lovastatin generic (LVSG), and a reference (mevinacor 40 MSD) preparation. The pharmacokinetics and bioequivalence of the two formulations of lovastatin were evaluated by a two-way cross-over randomized double blinded study, in 36 healthy volunteers after a single oral dose of 2 x 40 mg per subject. On plasma samples, collected at given intervals of time (0-24h), lovastatin and its main active metabolite were assayed by high pressure liquid chromatography with positive turbo ion spray ionization tandem mass spectrometry detection. The pharmacokinetic parameters, area under the curve total (AUC(t)) and to infinity (AUC(inf)), peak plasma concentration (C(max)), time to attain peak (t(max)), and elimination half-life (t(1/2)) were determined and analyzed statistically. Only minor differences in the pharmacokinetics of lovastatin and lovastatin hydroxyacid between LVSG and mevinacor were found. Analysis of variance (ANOVA) did not show any significant difference between the two formulations, and 90% confidence intervals fell within the acceptable range for bioequivalence. The tolerability profile was good and comparable for the two formulations of lovastatin. Our study, which was performed with the largest number of subjects compared with those published in literature, indicates the bioequivalence of LVSG and mevinacor tablets. The high inter-subject variability of parameters investigated indicate the need of appropriate sample size in pharmacokinetics studies with lovastatin.

Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?

Inhibition of endogenous acetylcholine degradation through cholinesterase inhibitors represents a milestone in symptomatic treatment of cognitive symptoms in mild to moderate stages of Alzheimer's disease. Cholinesterase inhibitors are also under investigation for treating cognitive dysfunction of cerebrovascular origin, but to date they do not have specific indication for vascular dementia or vascular cognitive impairment. This paper reviews the main clinical studies assessing the activity of cholinergic precursors in the treatment of adult-onset dementia disorders of vascular origin. The first cholinergic precursor used phosphatidylcholine (lecithin) did not show any clear clinical benefit on symptoms of dementia disorders. The same is not true for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) and choline alphoscerate for which a modest improvement of cognitive dysfunction in dementia of neurodegenerative and vascular origin is documented. Positive results obtained with selected cholinergic precursors cannot be generalized due to the small numbers of patients studied in appropriate clinical trials. However, they probably would justify reconsideration of the most promising molecules in larger carefully controlled studies.

Single-dose, randomized, crossover bioequivalence study of amlodipine maleate versus amlodipine besylate in healthy volunteers.

Amlodipine, marketed primarily as a besylate salt, is a calcium channel blocker used for treating essential hypertension. Amlodipine maleate is another salt that is considered, in terms of pharmacokinetics and pharmacodynamics, similar to amlodipine besylate. This open, randomized, two-period crossover trial has investigated in 24 healthy volunteers over a 144 h period the bioequivalence of amlodipine maleate tablets 10 mg versus amlodipine besylate tablets (Norvasc 10 mg). Plasma amlodipine concentrations were assessed by ultra performance liquid chromatography interfaced with a double quadrupole mass spectrometer. The area under the curve total (AUC(t)) and the area under the curve to infinity (AUC(inf)) values, peak plasma concentration (C(max)), and time to attain peak (t(max)) were not statistically different between the two drugs. AUC(t) and AUC(inf) values were higher (p < 0.05) in females than in males. The tolerability profile was comparable for the two salts of amlodipine. These findings indicate that amlodipine maleate and besylate are bioequivalent and were well tolerated, which suggests that the plasma kinetics of amlodipine depend on the properties of the molecule itself. Hence, the two salts investigated could be used interchangeably in clinical practice.

Comparative crossover, randomized, open-label bioequivalence study on the bioequivalence of two formulations of thioctic acid in healthy volunteers.

An open-label, randomized, crossover single-dose study, using two periods and two sequences with a washout period of seven days was conducted to assess the comparative bioavailability of thioctic (alpha-lipoic) acid (ALA) 600 mg formulation and that of a reference formulation. Blood samples were collected up to +6 h post dosing, the plasma was separated, and thioctic acid concentrations were determined by high-performance liquid chromatographic method with single mass spectrometry detection (HPLC-MS) and a lower limit of quantification of 190.1 ng/ml. Mean values of the individual C(max) were 1338.6 +/- 751.8 ng/ml and 1215.8 +/- 560.5 ng/ml for the test and reference preparations, respectively. Mean +/- standard deviation (SD) total area under the curve up to the last measurable concentration (AUC(t)) was 3510.9 +/- 1088.6 ng x h/ml for the test formulation and 3563.5 +/- 1374.1 ng x h/ml for the reference formulation. Mean +/- SD total area under the curve (AUC(inf)) was 6925.6 +/- 4045.8 ng x h/ml for the test formulation and 7797.1 +/- 5963.1 ng x h/ml for the reference preparation. Terminal elimination half-life was 5.68 +/- 5.05 h for the test and 6.11 +/- 6.15 h for the reference formulations. Time of maximum concentration (t(max)) was 1.24 +/- 1.23 h for the test and 2.05 +/- 1.21 h for the reference formulations. Ninety percent confidence intervals were comprised within the bioequivalence acceptance criteria (80-125%) for all of the parameters analyzed except t(max). The comparison between males and females showed no significant difference for the two drug treatment.

Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis.

AIM: To demonstrate clinical effectiveness of micronized palmitoylethanolamide-trans-polydatin combination in reducing endometriotic chronic pelvic pain. Other endometriotic-pains were also assessed. METHODS: Systematic reviews of PubMed, SCIELO, Scopus, and AJOL. Randomized trials and observational studies reporting a visual analogue scale for pain or similar in endometriotic patients were reviewed. A mean improvement of visual analogue scale (or visual analogue scale-like) scores at enrollment and at a three-month follow-up was assessed and interpreted clinically. RESULTS: Four studies of poor quality were available. In a heterogeneous sample of endometriotic patients with pain, the administration of micronized palmitoylethanolamide/trans-polydatin (400 mg/40 mg) twice a day for three months provided a clinically relevant improvement of chronic pelvic pain and dysmenorrhea while improving deep dyspareunia to a limited degree. No clinically relevant improvement was found for dyschezia. CONCLUSION: More studies are warranted for assessing the drugs-related efficacy.

Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats.

The influence of long term treatment with choline alphoscerate on microanatomy of hippocampus and glial reaction was assessed in spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is a cholinergic precursor, which has shown to be effective in countering cognitive symptoms in forms of dementia disorders of degenerative, vascular or combined origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical, immunochemical and immunohistochemical techniques associated with quantitative analysis. Treatment with choline alphoscerate countered nerve cell loss and glial reaction primarily in the CA1 subfields and in the dentate gyrus of the hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent changes in hippocampal microanatomy. Both compounds did not affect blood pressure values in SHR. These data suggest that choline alphoscerate may play a role in the countering hippocampal changes induced by cerebrovascular involvement. The observation that treatment with choline alphoscerate attenuates the extent of glial reaction in the hippocampus of SHR suggests also that the compound may afford neuroprotection in this animal model of vascular brain damage.

Causal assessment of pharmaceutical treatments: why standards of evidence should not be the same for benefits and harms?

It is increasingly acknowledged both among epidemiologists and regulators that the assessment of pharmaceutical harm requires specific methodological approaches that cannot simply duplicate those developed for testing efficacy. However, this intuition lacks sound epistemic bases and delivers ad hoc advice. This paper explains why the same methods of scientific inference do not fare equally well for efficacy and safety assessment by tracing them back to their epistemic foundations. To illustrate this, Cartwright's distinction into clinching and vouching methods is adopted and a series of reasons is provided for preferring the latter to the former: (1) the need to take into account all available knowledge and integrate it with incoming data; (2) the awareness that a latent unknown risk may always change the safety profile of a given drug (precautionary principle); (3) cumulative learning over time; (4) requirement of probabilistic causal assessment to allow decision under uncertainty; (5) impartiality; and (6) limited and local information provided by randomised controlled trials. Subsequently, the clinchers/vouchers distinction is applied to a case study concerning the debated causal association between paracetamol and asthma. This study illustrates the tension between implicit epistemologies adopted in evaluating evidence and causality; furthermore, it also shows that discounting causal evidence may be a result of unacknowledged low priors or lack of valid alternative options. We conclude with a presentation of the changing landscape in pharmacology and the trend towards an increased use of Bayesian tools for assessment of harms.

Postnatal development of dopamine receptor expression in rat peripheral blood lymphocytes.

Postnatal development in the expression of dopamine D1-like and D2-like receptors was investigated in peripheral blood lymphocytes of male Wistar rats aged 1, 3, 4, 8, 12 and 16 weeks of age by radioligand binding assay techniques. Sample of frontal cortex, striatum and hippocampus were also investigated as reference tissues. The dopamine D1-like receptor antagonist [3H]SCH 23390 and the dopamine D2-like receptor agonist [3H]7-OH-DPAT were used as radioligands. The affinity (K(d)) of [3H]SCH 23390 or of [3H]7-OH-DPAT binding was unchanged in lymphocytes of rats of different age groups. The density (B(max)) of [3H]SCH 23390 binding sites increased from the 1st to the 3rd week of age, remained constant from the 3rd to the 8th week of age, and then increased slightly at 12 and 16 weeks of age. The B(max) value of [3H]7-OH-DPAT binding to lymphocytes increased from the 1st to the 3rd week of age, remained constant from the 3rd to the 4th week, increased again until the 12th week and then plateaued. Dopamine D1-like and D2-like receptor maturation in frontal cortex, hippocampus and striatum revealed an increased receptor density until the 4th week of age and a relative stabilization of receptor density values between the 4th to the 12th week depending on the area considered. Comparatively postnatal maturation of lymphocyte dopamine D1-like receptors displayed a pattern different from that of brain areas investigated, whereas maturation of D2-like receptors displayed a pattern similar to that of striatum. The quantitative and/or qualitative dissimilarities between development of lymphocyte and brain dopamine receptors suggest that from a developmental point of view lymphocyte dopamine receptors probably cannot be considered as a marker of homologous brain receptors.