Search

Abstract—The aim of this short review was to collate the data involving the effects of lithium alone, or in combination, with antidepressant drugs in several animal models of depression. It has been shown that lithium administration reduced immobility in the mouse forced swimming test when given 30 min, but not 45 min, before testing. Further studies indicated that this activity was probably a result of an activity on serotonin (5‐HT) 1A and IB receptor subtypes. Lithium treatment has been shown to reverse helpless behaviour in the learned helplessness model of depression after chronic treatment (30 days), where lithium was administered in the drinking water. Further studies showed that acute (5 days) administration of lithium failed to reverse behavioural deficits. In the olfactory bulbectomised rat model of depression, several immunological and enzymatic functions have been shown to be altered and these changes are regularised by antidepressant treatment as well as lithium administration for 15 days. Hypokinesia (reduced locomotor activity) is a phenomenon observed following immobilisation stress in rats. This behavioural deficit was attenuated by lithium together with a wide range of antidepressant drugs used in the treatment of unipolar depression at non‐stimulant doses. In addition, a single administration of lithium slightly inhibited midbrain raphe lesion‐induced muricidal behaviour (25%); however, repeated treatment (5 days) significantly attenuated this behavioural deficit. Lithium treatment has also been shown to reverse behavioural and biochemical deficits induced by reserpine together with those induced by acute administration of single intracerebroventricular (i.e.v.) dose of the Na, K‐ATPase‐inhibiting compound, ouabain. Long‐term studies of lithium augmentation have not been performed, so that no clear recommendations for the duration of this therapy can be made. The points raised in this short review endorse the commencement of such studies.

This study was undertaken to evaluate the efficacy of standard neuroleptic treatment versus depot neuroleptic treatment. The major criterion for evaluation was the number of patients hospitalized. Patients were chosen on the basis of their rating by the ICD-10 classification for schizophrenic disorders. The first study period was defined as the time when patients were treated with standard neuroleptics; the second was when patients were treated with depot neuroleptics. There were 231 hospitalizations during the first period, which involved 48 patients, i.e. 4.8 hospitalizations per patient. The mean total duration of these hospitalizations was 5.2 years, i.e. it was on average 5 years before the patient was treated with a depot neuroleptic, with 0.93 hospitalizations per year. The duration of the second period was the same as the first. Only 44 patients remained in the study during this period; their mean number of hospitalizations was 7.2 per patient. The mean number of hospitalizations per year per patient was 1.25. The results suggest that the number of hospitalizations is only a partially satisfactory way of evaluating the efficacy of neuroleptic treatments, and questions the relative efficacy of depot neuroleptics compared with standard neuroleptic treatment.

This study investigated a role of cholecystokinin (CCK) in the anxiolytic-like action of morphine, an agonist of μ-opioid receptors, in the rat plus-maze model of anxiety. The acute administration of morphine (1 mg/kg) induced a significant increase of exploratory activity in the plus-maze, but did not affect the locomotor activity in the motility test. The higher dose of morphine (2.5 mg/kg) tended to decrease the locomotor activity and, therefore, did not cause the anxiolytic-like action in the plus-maze. The other drugs (naloxone, BOC-CCK-4, L-365,260) and their combinations with morphine (0.5–1 mg/kg) did not affect the locomotor activity of rats. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity in the plus-maze, but potently antagonized the anxiolytic-like action of morphine (1 mg/kg). An agonist of CCKBreceptors BOC-CCK-4 (1–50 μg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze. Nevertheless, only one dose of BOC-CCK-4 (10 μg/kg) completely reversed the action of morphine. Also, one dose of CCKBreceptor antagonist L-365,260 (10 μg/kg) was effective to modify the behaviour of rats in the elevated plus-maze. Namely, this dose of L-365,260 increased the ratio between open and total arm entries, a behavioural measure believed to reflect the anxiolytic-like action in the elevated plus-maze. The combination of L-365,260 (100 μg/kg) with the sub-effective dose of morphine (0.5 mg/kg) caused the anxiolytic-like action in the plus-maze not seen if the drugs were given alone. In conclusion, morphine induces a potent anxiolytic-like action in the elevated plus-maze and CCK is acting as an endogenous antagonist of this effect of morphine.

The present study was designed to evaluate the psychopharmacological profile of the selective serotonin reuptake inhibitor paroxetine, and thus assess potential noradrenergic and/or serotonergic activity. Paroxetine dose-dependently increased mobility time in the mouse forced swimming test (8, 16, 32 and 64 mg/ kg, i.p.) and reduced spontaneous locomotor activity when administered at a high dose (64 mg/kg, i.p.). Prior administration of 8-hydroxy-2-(di-n-propylamino)tetralin (1 mg/kg, i.p.), (±) pindolol (32 mg/kg, i.p.) or 5- methoxy-3-(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, i.p.) potentiated the antidepressant- like effects of subactive doses of paroxetine (1, 2 and 4 mg/kg, i.p.) in the mouse forced swimming test. These effects were antagonized by prior administration of 1-(2-methoxyphenyl)-4-[-(2-phthalimido)butyl]piperazine) (0.5 mg/kg, i.p.). Complementary studies suggested that RU24969-induced anti-immobility effects were a result of an increase in locomotor activity; other interactions were without increase/decrease in locomotor activity. Acute administration of paroxetine (8,16, and 32 mg/kg, i.p.) antagonized the hypothermia induced by the D2/D1receptor agonist, apomorphine (16 mg/kg, s.c.), while repeated treatment with paroxetine (32 mg/kg) attenuated clonidine-induced (0.5 mg/kg, i.p.) hypothermia. Pre-treatment with the serotonergic neurotoxin, parachlorophenylalanine attenuated the anti-immobility effects of low doses of paroxetine (8 and 16 mg/kg, i.p.) in the forced swimming test, whereas a higher dose of paroxetine remained active (32 mg/kg, i.p.). The results of the present study indicated that paroxetine displayed both noradrenergic-like and serotonergic-like activity in the pre-clinical psychopharmacological tests employed.

The effects of lorazepam (0.25 mg) twice a day on several cognitive and performance tasks, pictures test, digit-symbol substitution test (DSST), choice reaction time (CRT) and critical flicker fusion (CFF), were investigated in healthy students. A double-blind independent group design was used to compare placebo and lorazepam (30 volunteers in each group). After randomisation, all subjects received placebo for 3 days (D), followed by 14 days of treatment, with either lorazepam or placebo. Subjects completed a battery of tests at Do, then D3, D7, D10and D14. D3performance was poorer in the lorazepam group except for CFF (ascending values and total values), yet the only significant improvement was in total reaction time on the CRT test. However, a significant improvement of performance was shown at D7, D10and D14in the lorazepam group compared with the control group (except in recognition reaction time). The current study shows that low repeated doses of lorazepam are able to produce small improvements in some aspects of psychomotor and cognitive functions in healthy volunteers. Different points are discussed to explain the performance improvement: training effect, tolerance effect, partial inverse agonist effect and the possible release of cholecystokinin.

A new conflict procedure was developed to study the potential anti-punishment effects of 5-HT1Aagonists as compared to diazepam. In this paradigm, the opportunity existed for rats to choose during punished periods between immediate, punished reinforcement and delayed, non-punished reinforcement. The results confirm that, for non-sedative doses (1 mg/kg), diazepam increases the number of punished responses. Furthermore, the present paradigm seems sensitive for the detection of 5-HT1Aactivity. Buspirone, gepirone, ipsapirone, zalospirone and 8-OH-DPAT increased responding for immediate but punished reinforcement. 1-(2-pyrimidinyl)piperazine, the common metabolite of the azapirones, does not participate in their anti-conflict effect. NAN 190, a 5-HT1Aantagonist, was shown to block the 5-HT1Aagonists. The findings of the present study suggest that benzodiazepines and 5-HT1Aagonists reduce the capacity to tolerate delays in reward. Abnormality in serotonin systems may be associated with poor impulse control.

Rabbit thrombomodulin displays three distinct blood anticoagulant activities: it promotes the activation of protein C by thrombin (protein C activation cofactor activity); it promotes the inactivation of thrombin by thrombin (direct anticoagulant activity). The effects on these activities of mouse anti-thrombomodulin monoclonal antibodies and of the heparin-neutralizing proteins, platelet factor 4, histidine-rich glycoprotein, and S-protein, were investigated. One of the antibodies, which did not influence the functional properties of thrombomodulin, was used as an immunoaffinity ligand for purification of the protein. Two other antibodies, which were found to abrogate the protein C activation cofactor activity of the purified thrombomodulin, also abolished the antithrombin-dependent and the direct anticoagulant activities. The heparin-neutralizing proteins all inhibited the two latter activities, albeit to a varying extent, but did not appreciably affect the activation of protein C. These results are interpreted in relation to our previous finding that rabbit thrombomodulin contains an acidic domain, tentatively identified as a sulfated glycosaminoglycan (Bourin, M.-C., Boffa, M.-C., Björk, I., and Lindahl, U. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5924-5928). It is proposed that the acidic domain interacts with thrombin at the protein C activation site and that this interaction is a prerequisite to the expression of direct as well as antithrombin-dependent anticoagulant activity. The interaction is not essential to, but compatible with, the activation of protein C. Experiments involving treatment of thrombomodulin with various glycanases or with nitrous acid, followed by measurement of anticoagulant activities, indicated that the acidic domain is constituted by a sulfated galactosaminoglycan and not by a heparin-related polysaccharide as previously suggested.

In neuroleptic therapy for psychotic illnesses, clinical improvement occurs much later than central dopamine blockade, and its time course varies widely among patients. A hypothesis explaining neuroleptic-responsive illness cannot be explained by dopamine blockade alone. Nevertheless, experimental data suggest that this mechanism may be a step in the therapeutic process for schizophrenia. Explanations are suggested for the time lag in therapeutic response for neuroleptics, including the hypothesis of delayed inactivation of mid-brain dopamine neurones.Chronic benzodiazepine treatment elicits adaptive responses in the CNS that are manifested as functional tolerance and physical dependence. Possible mechanisms involved in such a profound alteration of neuronal functioning are suggested. Down regulation of benzodiazepine receptors has been shown to be related to functional tolerance under certain conditions.The effect of repeated treatment with antidepressants is compatible with the hypothesis that changes in central monoamine transmission are involved in the activity of these drugs. Beta-adrenergic receptors are desensitized and their density is decreased; alpha-2 adrenoreceptors sensitivity is reduced, and post-synaptic serotoninergic receptors sensitivity is increased. It remains to be clarified whether some of the changes have larger role than others or whether they all contribute to the psychotropic drug activity in the therapeutic process.

Objectif Expliquer à l'aide d'études animales le mode d'action des psychostimulants.Méthode Une revue de la littérature psychiatrique sur l'usage des psychostimulants chez l'enfant et l'adulte.Résultats En étudiant la littérature psychiatrique, il s'avère que 50 ans après l'introduction de l'amphétamine en clinique, les psychostimulants sont des médicaments utilisés, notamment le méthylphénidate, dans le traitement de l'hyperactivité de l'enfant avec ou sans déficit de l'attention. En revanche, chez l'adulte les psychostimulants cherchent encore leur voie, malgré des études dans le traitement de la dépression et d'autres maladies mentales. Seule la narcolepsie semble être justifiable de tels produits.Conclusion La preuve est largement faite de l'utilité des psychostimulants chez l'enfant. Chez l'adulte, ils pourraient être utiles à condition de mieux étudier les symptômes cibles.

Thrombomodulin isolated from rabbit lung was separated by ion-exchange chromatography on DEAE-cellulose into a retarded (acidic) and a nonretarded (nonacidic) fraction. Both fractions contained the cofactor required for the activation of protein C. In addition, the acidic fraction (but not the nonacidic fraction) prevented the clotting of fibrinogen by thrombin ("direct" anticoagulant activity) and accelerated the inhibition of thrombin by antithrombin (effect corresponding to 2-10 international units of heparin per mg of protein). Both of these activities were readily neutralized by the synthetic polycation Polybrene, which did not appreciably affect protein C activation. They were also eliminated by digestion of thrombomodulin with bacterial heparinase, which, in addition, converted the acidic form of the protein C activation cofactor to a nonacidic form. Similar conversion observed during storage of thrombomodulin was attributed to endogenous proteinase activity. Density-gradient centrifugation of the acidic form of thrombomodulin in CsCl/4M guanidinium chloride failed to separate either of the direct or antithrombin-dependent anticoagulant activities from the protein C activation cofactor, which showed a buoyant density of 1.31-1.34 g/ml. The nonacidic cofactor had a lower density, 1.26-1.28 g/ml. Unreduced thrombomodulin yielded two major fractions of protein C activation cofactor on NaDodSO4/PAGE, with apparent Mr of approximately 68,000 and 57,000, respectively. The larger component contained essentially all of the direct and antithrombin-dependent anticoagulant activities. We propose that these activities as well as the negative charge and the higher buoyant density of the acidic, Mr 68,000 form of thrombomodulin are due to a heparin-like polysaccharide and, further, that this component can be separated from the major portion of the molecule, which contains the protein C activation site, through the action of a proteinase.

Heparin and heparan sulfate proteoglycans (HSPGs) stabilize FGFs which belong to heparin-binding growth factors (HBGFs) on active conformation. They also strongly potentiate their mitogenic activity on many cell types, and protect them against thermal denaturation and enzymatic degradation. In the present work we have tested two heparin-like substances named mesoglycan and sulodexide obtained from bovine intestinal mucosal extracts. These products are used as heparin, in various of therapeutic fields such as atherosclerosis or antithrombotic therapy. The compositions of mesoglycan and sulodexide are partially known and include chondroitin, dermatan and heparan sulfate. We have shown that mesoglycan and sulodexide potentiated the mitogenic activity of FGF1 and FGF2. The magnitude of this effect was identical with that of heparin used as a control substance but at double concentration. Mesoglycan and sulodexide also exerted stabilizing and protective effects on FGFs for heat denaturation and enzymatic degradation. The suppression of the protective properties after heparinase treatment of mesoglycan and sulodexide indirectly demonstrated the presence of heparan sulfate which was shown to represent about 60% of the commercial products.

Thrombomodulin (TM), a major anticoagulant protein at the vessel wall, serves as a potent cofactor for the activation of Protein C by thrombin. Previous work has indicated that (rabbit) TM is a proteoglycan that contains a single polysaccharide chain, tentatively identified as a sulphated galactosaminoglycan, and furthermore suggested that this component may be functionally related to additional anticoagulant activities expressed by the TM molecule [Bourin, Ohlin, Lane, Stenflo & Lindahl (1988) J. Biol. Chem. 263, 8044-8052]. Results of the present study establish that (enzymic) removal of the polysaccharide chain abolishes the inhibitory effect of TM on thrombin-induced fibrinogen clotting as well as the promoting effect of TM on the inactivation of thrombin by antithrombin, but does not affect the ability of TM to serve as a cofactor in the activation of Protein C. Studies of yet another biological activity of rabbit TM, namely the ability to prevent the activation of Factor V by thrombin [Esmon, Esmon & Harris (1982) J. Biol. Chem. 257, 7944-7947], confirmed that TM markedly delays the conversion of the native 330 kDa Factor V precursor into polypeptide intermediates, and further into the 96 kDa heavy chain and 71-74 kDa light-chain components of activated Factor Va. In contrast, the activation kinetics of a similar sample of Factor V incubated with thrombin in the presence of chondroitinase ABC-digested TM did not differ from that observed in the absence of TM. It is concluded that the inhibitory effect of TM on Factor V activation also depends on the presence of the polysaccharide component on the TM molecule.

THE action of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) (1–20 mg kg-1) on the exploratory behaviour of rats in the elevated plus-maze was studied. L-NAME induced an anxiolytic-like effect in the plus-maze test, showing a reverse U-shape action behaviour, with a maximal effect at 10 mg kg-1. This effect was not related to a non-specific increase in motor activity, since in the open field test L-NAME did not affect locomotor activity of rats. Pretreatment of rats with L-NAME (1–10 mg kg-1) also tended to attenuate the anti-exploratory action of CCK agonist caerulein (5 mUg kg-1), but this action was not significant. In conclusion, it appears that NO may be involved in the process that can lead to anxiety in the rat.

Summary—The aim of the present study was the investigation of pretreatment effects with clonidine (0.06 mg/kg, intraperitoneal [ip]), lithium (1 mEq, ip) or quinine (0.5 mg/kg, ip) on the activities of various drugs acting on noradrenergic and/or serotonergic systems in the mouse tail suspension test. Drugs used in the present study included: the tricyclic antidepressants imipramine and dothiepin, the heterocyclic antidepressant trazodone, the 5‐HT reuptake inhibitor (SSRI) fluoxetine, the atypical antidepressants mianserin and iprindole, the 5‐HT1Areceptor agonist ipsapirone, the 5‐HT2A/2Creceptor antagonist ritanserin, and the 5‐HT3receptor antagonist ondansetron. Clonidine, lithium and quinine differentially enhanced the effects of several psychotropic drugs administered at sub‐active doses. The activity of iprindole (32 mg/kg, ip) was not potentiated by pretreatment with clonidine, lithium or quinine. Our results suggest that lithium exerted additive effects via postsynaptic 5‐HT1Areceptor activation, quinine via potassium ion channel blockade of 5‐HT3receptors, while clonidine did so primarily via action at 5‐HT2receptors.

Activation, proliferation and circulation of immune cells vary predictably according to circadian (approximately 24-hour) rhythms. These biological rhythms are endogenous and genetically based. Rhythms in nocturnally active experimental animals such as mice or rats are 12 hours out of phase from those in diurnally active humans. In animal studies, the toxic and immunomodulatory effects of agents such as interferon, interleukin-2 and cyclosporin can vary by 50% or more according to time of administration, presumably as a result of circadian rhythms. Immunological circadian rhythms appear to be maintained in liver transplant patients receiving continuous infused immunosuppressive therapy. However, rhythms were altered in patients with advanced stage malignancy or HIV infection, and in cancer patients receiving infusions of cytokines on a standard regimen. Translation of these preclinical and clinical findings to drug delivery has just begun. A portable programmable-in-time pump was used to modulate delivery of interferon-a to patients with renal cell cancer. Maximal delivery was from 1800 to 2400h, with no delivery from 0600 to 1200h. Dosages of 15 to 20 MU/m2/day for 21 days were tolerated, 2 to 3 times higher than dosages administered using a standard regimen. Further trials of chronobiologically modulated therapy are warranted to establish its effectiveness in treatment of immunological disorders.

Previous studies on rabbit thrombomodulin (TM) revealed that certain anticoagulant activities expressed by TM depend on the presence of an acidic domain tentatively identified as a sulfated galactosaminoglycan (Bourin, M.-C., Ohlin, A.-K., Lane, D., Stenflo, J., and Lindahl, U. (1988) J. Biol. Chem. 263, 8044-8052). The glycan was released by alkaline beta-elimination, isolated by ion-exchange chromatography, and radiolabeled by partial N-deacetylation (hydrazinolysis) followed by re-N-[3H]acetylation. The labeled product behaved like standard chondroitin sulfate on ion-exchange chromatography, exhibited a Mr of 10-12 x 10(3) on gel chromatography, and was susceptible to degradation by chondroitinase and testicular hyaluronidase. The major labeled degradation products following digestion of the glycosaminoglycan with chondroitinase were identified, depending on the incubation conditions, either as 4/6-mono-O-sulfated, 4,5-unsaturated disaccharides (delta HexA-GalNAc(S] and N-acetylgalactosamine 4,6-di-O-sulfate (GalcNAc (diS], the latter component accounting for approximately 25% of the total label, or as a major fraction of labeled trisaccharide, with the predominant structure GalNAc(diS)-GlcA-GalNAc(diS). The terminal GalNAc(diS) unit (not substituted at C3) was shown to be more susceptible to N-deacetylation during hydrazinolysis than were the internal GalNAc units (substituted at C3), and thus was more extensively labeled, resulting in over-representation of this unit. It is concluded that rabbit TM is a chondroitin sulfate proteoglycan, which carries a single glycan side chain characterized by an unusual accumulation of sulfate groups at the nonreducing terminus. Metabolically 35S-labeled TM was isolated from cultured rabbit heart endothelial cells and characterized as a chondroitin sulfate proteoglycan which accounted for 1-2% of the total 35S-labeled cell-associated macromolecules. The isolated chondroitin sulfate showed weaker antithrombin-dependent anticoagulant activity, on a molar basis, than the intact TM proteoglycan. The anticoagulant action of TM thus depends on a unique form of functional collaboration between the different constituents of a glycoconjugate.

Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3−−CD16+, CD3−−CD57+, and CD2+CD3−−. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchro-nizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.

The effects of low oral doses of lorazepam on several cognitive and performance tasks were investigated in 50 healthy students. A double-blind, parallel group design was used to compare five treatments: placebo and lorazepam 0.5, 0.75, 1 mg and progressive doses up to 1.5 mg. After randomization, all subjects received placebo for 3 days in a single-blind procedure followed by five consecutive days of treatment. Subjects completed a battery of tests each day of the 5 days active treatment and the day after stopping the treatment. There were no significant differences between placebo and lorazepam on the free recall test and the critical flicker fusion frequency test, but lorazepam produced significant improvement on the digit symbol substitution test and the choice reaction time test. We suggest that low repeated doses of lorazepam in healthy subjects improve the psychomotor performance without sedation and memory impairment.

It has been suggested that cholecystokinin, a neurotransmitter found in high density in mammalian brain, might be implicated in the neurobiology of panic and anxiety disorders. Cholecystokinin-tetrapeptide induces panic attacks analogous to spontaneous panic attacks in patients suffering from panic disorder and to a much lesser degree in healthy volunteers, suggesting an enhanced sensitivity to cholecystokinin-tetrapeptide in panic disorder. In animal models of anxiety, pre-treatment with cholecystokinin antagonists significantly decreases the anxiogenic effects of cholecystokinin agonists. This paper reviews clinical and basic studies supporting an involvement for cholecystokinin in panic and anxiety disorders.

Summary—Euphytose (EUP) is a combination of six extracts: Crataegus, Ballota, Passifloraand Valeriana, which have mild sedative effects, and Colaand Paullinia, which mainly act as mild stimulants. This multicenter, double‐blind, placebo‐controlled general practice study was carried out in outpatients with ajustment disorder with anxious mood. The study was coordinated by psychiatrists. Ninety‐one patients were included in the EUP group and 91 patients in the placebo group. They all received two tablets three times a day over 28 days (D). Evaluation using the Hamilton‐anxiety (HAM‐A) rating scale were carried out on D0, D7, D14 and on D28. Comparing the two groups, 42.9% of the patients (EUP group) had a HAM‐A score of less than 10 at D28 versus 25.3% in the placebo group (P= 0.012). Changes in the HAM‐A score between D0 and D28 were as follows: D0 (EUP: 26.12 ± 4.0, placebo: 26.27 ± 4.5), D7 (EUP: 19.65 ± 5.7, placebo: 21.37 ± 5.6), D14 (EUP: 15.36 ± 5.7, placebo: 17.48 ± 6.7), D28 (EUP: 12.63 ± 7.3, placebo: 15.2 ± 8.1). From D7 to D28 there was a statistically significant difference (P= 0.042) between the two treatments, indicating that EUP is better than placebo in the treatment of adjustment disorder with anxious mood.

Antisera raised against galectin-1 exhibit crossreactivities with other galectins or related molecules. In order to overcome this problem, a monoclonal antibody to human brain galectin-1 was obtained by selecting clones without reactivity toward galectin-3. This mAb specifically bound galectin-1 of various animal origins but neither galectin-2 nor galectin-3. Western-blotting analysis of soluble human brain extracts after 2D gel electrophoresis revealed only the two most acidic isoforms of galectin-1. The ability of this mAb to bind galectin-1/asialofetuin complexes indicates that its epitope is not localized in the carbohydrate recognition domain of galectin-1. This particularity induces with efficiency its monospecificity.