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Biomedical subjects

J Palermo-Neto

Publications and source records attributed to J Palermo-Neto.

At least 19 recordsLinked to original sources

Variations in behavior, innate immunity and host resistance to B16F10 melanoma growth in mice that present social stable hierarchical ranks.

The present study analyzed the effect of social stable hierarchical dominance/submissive relationships in C57BL/6 mice on behavior, innate immunity, serum corticosterone levels and host resistance to B16F10 melanoma growth. Adult mice (90 days old) kept in pairs since weaning, were analyzed for dominant/submissive ranking in three consecutive days according to the presence or absence of fighting and/or anticipatory submissive responses. Only the pairs of mice where dominant/submissive relationships were clearly stated were employed. Results showed that submissive mice presented in relation to dominants: (1) decreased time spent in the central open-field area; (2) decreased number of entries into the open arms and decreased time spent in the exploration of the open arms of the plus maze; (3) increased time spent in exploration of the plus-maze closed arms; (4) decreased number of entries and in the time spent in the exploration of the third part of the plus-maze open arms; (5) increased number of B16F10 metastasis in the lungs; (6) decreased NK cell cytotoxicity measured in vitro in the peripheral blood and spleen; (7) decreased basal but not in S. aureus induced oxidative burst in both neutrophils and monocytes and (8) similar basal serum levels of corticosterone. The present behavioral findings show that submissive mice, within a stable social hierarchy, present anxiety like-responses a fact that would make than more prone to stressful stimuli. This condition would be responsible for the decreases presently observed on basal neutrophil oxidative burst, NK cell activity and resistance to B16F10 tumor growth. Together the obtained data show that mice that present stable hierarchical relationships display neuro-immune alterations comparable to those reported in mice under a situation of chronic social stress.

Animals↗

Diazepam effects on Ehrlich tumor growth and macrophage activity in mice.

Besides the central gabaergic receptors described for benzodiazepines, peripheral type binding sites (PBR) were also identified for these molecules in endocrine steroidogenic tissues, immune organs and cells, such as macrophages and lymphocytes. PBR activation was reported to decrease innate immunity and host defense. The present experiment was designed to analyze the effects of diazepam on Ehrlich tumor growth, and on macrophage activity of Ehrlich tumor bearing mice. Results showed that diazepam (3.0 mg/kg/day, for 7 days) increased the number of Ehrlich tumor cells and the volume of tumor-induced ascitic fluid. These effects were not observed after smaller doses of diazepam, suggesting a dose-dependant effect. Furthermore, our results show that 3.0 mg/kg of diazepam, administered daily, for 2 days, decreased (1) the number of peritoneal leukocytes retrieved after injection of the Ehrlich tumor, (2) the percents of macrophage spreading, and (3) the levels of macrophage NO production. Diazepam (3.0 mg/kg/day for 2 days) had no effect on macrophage phagocytosis or on H2O2 production. The present data is discussed based on a direct and/or indirect action of diazepam. Particularly, our findings might be due to a direct effect of diazepam on PBRs present on macrophages and tumor cells, or could still be mediated by PBR stimulation within the hypothalamus-pituitary-adrenal (HPA) axis.

Animals↗

Effects of type II pyrethroid cyhalothrin on peritoneal macrophage activity in rats.

Synthetic type II pyrethroids induce anxiety, immunosuppressive or, alternatively, immunostimulatory effects in laboratory animals. Macrophages are known to be key elements in cellular immune responses. The present study was designed to investigate the in vivo effects of cyhalothrin (0.6, 1.0 and 3.0 mg/kg/once daily for 7 days) on macrophage activity. The in vitro effects of cyhalothrin (100 nM, 1 and 10 microM) were also analyzed to verify a possible direct action of this pyrethroid on macrophage. Results showed that in vivo cyhalothrin treatment: (1) decreased macrophage spreading and phagocytosis indexes; (2) decreased macrophage nitric oxide (NO) production; (3) did not change spontaneous or PMA-induced macrophage H2O2 release. The no effect level dose (NOEL) obtained for cyhalothrin on macrophage activity was 0.6 mg/kg/day. In-vitro data showed that cyhalothrin decreased (1) macrophage NO production and (2) macrophage spontaneus and PMA-induced H2O2 releases. The present results were explained through an indirect action for cyhalothrin on macrophage activity via hypothalamic pituitary adrenals (HPA) axis activation. A direct effect for cyhalothrin on macrophage, most probably through an action on Na+ membrane channels, was also suggested. Finally, it is possible that both direct and indirect mechanisms would be involved with cyhalothrin effects on macrophage activity.

Animals↗

Haloperidol treatments increased macrophage activity in male and female rats: influence of corticosterone and prolactin serum levels.

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.

Animals↗

Monosialoganglioside (GM1) attenuates the behavioural effects of long-term haloperidol administration in supersensitive rats.

In the present study we investigated the effects of co-administration of GM(1) (15.0 mg/kg, twice daily, for 30 days) and haloperidol (1.0 mg/kg, twice daily, for 30 days), as well as the effects of a 5-day treatment with this dose of GM(1) after withdrawal from haloperidol in rats. The animals were evaluated in the open-field test and apomorphine-induced stereotyped behaviour. The results show that GM(1) was able to attenuate dopaminergic supersensitivity evaluated by the locomotion frequency at 24 and 48 h after the withdrawal from haloperidol. On the other hand, rearing frequency was changed neither by haloperidol nor by GM(1.) In haloperidol-treated rats immobility time differs from 30 min observation session in comparison with the following sessions after the withdrawal from neuroleptic. Apomorphine-induced stereotyped behaviour produced a significant increase in scores of haloperidol-withdrawn rats. GM(1) did not modify the haloperidol effects and did not change the dopamine receptor affinity to apomorphine 100 h from abrupt neuroleptic withdrawal.

Analysis of Variance↗

Effects of amphetamine on immune-mediated lung inflammatory response in rats.

OBJECTIVE: The present study analyzed the effects of acute amphetamine (AMPH) treatment on immune-mediated lung inflammatory response in rats. METHODS: There were four experiments. In the first and second experiments, rats were treated with AMPH (1 mg/kg) or 0.9% NaCl, and locomotor activity (experiment 1) and serum AMPH concentrations (experiment 2) were measured 1 or 12 h after treatment. In the third experiment, rats which were immunized with ovalbumin (OVA) were treated 14 days later with 0.9% NaCl or AMPH (1 mg/kg). Twelve hours after these treatments, all animals were submitted to challenge by 1% OVA inhalation being analyzed afterwards for bronchoalveolar lavage fluid (BAL), peripheral blood and bone marrow cellularity. In the fourth and final experiment, rats were treated and studied as for experiment 3, except that half of the animals within each group were previously treated with metyrapone prior to the OVA challenge. RESULTS: In the non-immunized rats, AMPH treatment induced an increase in locomotor activity synchronized to high serum AMPH concentrations 1 h after, but not 12 h after treatment. In OVA-challenged rats, AMPH treatment decreased the total number of inflammatory cells, recovered in both BAL and peripheral blood and increased the total number of bone marrow cells. These effects, observed 1 day after OVA challenge, were abrogated by previous metyrapone treatment. CONCLUSION: AMPH treatment changed HPA-axis responsiveness to the stress condition imposed by the OVA challenge decreasing lung and blood leukocytes cellularity most probably via corticosterone actions on bone marrow activity.

Amphetamine↗

Effects of midazolam on equine innate immune response: a flow cytometric study.

Benzodiazepines (BDZ) are among the most frequently used class of psychotropic drugs employed in veterinary medicine in Brazil and worldwide due to their anxiolytic, muscle relaxant and anticonvulsant effects [J. Clin. Pharmacol. 33 (1993) 124]. Peripheral benzodiazepine receptor (PBR) sites were described in peripheral organs, endocrine steroidogenic tissues and immune organs and cells. Midazolam is a mixed-type agonist of PBRs. The present study is focused on the effects of midazolam on equine peripheral blood neutrophils, peritoneal macrophages and cortisol levels in plasma. Adult horses were treated with a single dose of midazolam (0.06 or 0.1 mg/kg) or with 0.9% NaCl. Immune cells were collected 24 h after treatment for flow cytometry analysis of Staphylococcus aureus-induced phagocytosis and oxidative burst. Plasma cortisol concentration was measured 30, 90, 180 and 360 min after midazolam treatment. Midazolam induced a dose-dependent reduction on: (1) peripheral blood neutrophil and peritoneal macrophage oxidative burst; (2) the capacity of both peripheral blood neutrophils and peritoneal macrophages to phagocyte S. aureus. Increments on plasma cortisol concentration were not found after 0.06 and 0.1 mg/kg of midazolam. The effects on oxidative burst of neutrophils and macrophages from horses treated with midazolam were interpreted as a consequence of an impairment of S. aureus-induced phagocytosis. The present data suggest that midazolam, most probably acting on PBRs present on equine macrophage and neutrophil membranes, might have changed some mechanisms related to both phagocytosis and oxidative burst. These results support the use of flow cytometry to identify functional properties and dysfunction of equine immune cells. They also confirm the notion that changes in the functional capacity of the immune system may represent an important hazard of exposure to drugs or chemicals.

Anesthetics, Intravenous↗

Behavioral effects of type II pyrethroid cyhalothrin in rats.

Synthetic pyrethroids such as cyhalothrin are extensively used in agriculture for the control of a broad range of ectoparasites in farm animals. It has been suggested that type II pyrethroids might induce anxiogenic-like effects in laboratory animals. The present study was undertaken to investigate a possible anxiogenic-like outcome of cyhalothrin in rats. Adult male rats were orally dosed for 7 days with 1.0, 3.0, or 7.0 mg/kg/day of cyhalothrin, present in a commercial formulation (Grenade Coopers do Brazil S.A.). The neurobehavioral changes induced by cyhalothrin as well as those produced on corticosterone serum levels were measured 24 h after the last treatment. Picrotoxin (1.0 mg/kg) was also acutely used as a positive control for anxiety. Results showed that cyhalothrin: (1) induced some signs and symptoms of intoxication that included salivation, tremors, and liquid feces; (2) reduced total locomotor activity in the open-field; (3) reduced the percentage of time spent in open-field central zones; (4) increased immobility time in the open-field; (5) reduced the percentage of time spent in plus-maze open arms exploration; (6) reduced the time spent in social interactions, and (7) increased the levels of serum corticosterone. The behavioral changes reported for cyhalothrin (3.0 mg/kg/day) were similar of those induced by picrotoxin. The no effect level dose obtained for cyhalothrin in this study was 1.0 mg/kg/day. These results provide experimental evidence that cyhalothrin induces anxiety-like symptoms, with this effect being dose-related. Thus, anxiety must be included among the several signs and symptoms of pesticide intoxication.

Administration, Oral↗

Effects of prenatal stress on stress-induced changes in behavior and macrophage activity of mice.

The present study analyzed the effects of maternal stress on behavior and macrophage activity of mice. Pregnant mice received a daily footshock (0.2 mA) from gestational days 15 (GD15) to 19. Experiments were performed on male offspring, challenged or not with another footshock (0.2 mA) on postnatal day 30 (PND30) or 60. The following results were obtained for maternal stress: (1) increment in locomotor activity of juvenile but not of adult mice observed in both open-field and plus-maze; (2) increment in rearing frequency of juvenile but not of adult mice observed in the open-field; (3) decrement in macrophage spreading of adult but not of juvenile mice; (4) abolishment of postnatal footshock effects in both macrophage spreading on PND30 and macrophage nitric oxide (NO) production on PND60; (5) reversion of postnatal footshock effects on H(2)O(2) spontaneous and PMA-induced release by macrophage on PND30; (6) modification of postnatal stress effects on macrophage phagocytosis on PND60. These changes were unrelated to differences in gestational parameters and did not reflect altered maternal-pup interactions or nutritional factors. The observed data provide experimental evidence that maternal stress alters behavior, and macrophage activity at the same time and in the same litter. These data were discussed in the light of possible neuroimmune interactions that involve catecholaminergic pathways.

Animals↗

Stress-induced increment on total bronchoalveolar cell count in OVA-sensitized rats.

The influence of stress on total leukocyte count from bronchoalveolar lavage (BAL) was investigated in rats sensitized and challenged with ovalbumin (OVA). The animals were injected intraperitoneally with a suspension of OVA plus aluminum hydroxide in 0.9% NaCl (Day 0) and boosted at Day 7 with an identical OVA solution, administered subcutaneously. From the first to the 13th day after sensitization, rats were placed individually in a shuttle box where they received 50 escapable footshocks per day, always preceded by a sound signal (S); the responses that occurred during both S and shocks canceled the stressful stimulation. On Day 14, animals were submitted to a single session of 50 inescapable footshocks, preceded by the same S; immediately after, the animals were submitted to a 1% OVA-inhalation challenge. Results showed high levels of stress in the shocked animals as detected through both ultrasonic vocalizations (UVs) and social interaction test in an open field. Total leukocyte count in BAL from stressed animals (24 h post-OVA challenge) revealed a significant increase in the number of inflammatory cells in comparison to that measured in sensitized, nonstressed challenged rats. These data demonstrate that stress plays a relevant and important role on total bronchoalveolar cell count in OVA-sensitized rats.

Animals↗

Reduction of acute inflammation in rats by diazepam: role of peripheral benzodiazepine receptors and corticosterone.

Carrageenin causes a reproducible inflammatory reaction and remains the standard irritant for examining acute inflammation and anti-inflammatory drugs. High doses of diazepam (10.0-20.0 mg/Kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenin administration. The present experiment was undertaken to investigate the possible roles of peripheral-type benzodiazepine receptors (PBRs) and corticosterone on the anti-inflammatory effects of diazepam. Five experiments were conducted to assess the effects of a single dose (10.0 mg/Kg) of diazepam on carrageenin-induced paw edema (CIPE), pleurisy and increase in vascular permeability in rats. Results showed that: 1. diazepam or Ro5-4864 (a PBR agonist) treatment reduced CIPE values; 2. prior treatment with PK11195 (a non-benzodiazepine PBR antagonist) suppressed the effects of either diazepam or Ro5-4864 on CIPE; 3. diazepam reduced the volume of the pleural exudate in carrageenin-injected rats, as well as its leukocyte count; 4. diazepam treatment reduced the magnitude of the increase in vascular permeability caused by carrageenin; 5. adrenalectomy suppressed the effects of diazepam on CIPE; and 6. diazepam treatment increased the serum concentration of corticosterone. These results suggest a relevant role of PBR and corticosterone on diazepam-induced changes in inflammation. They are discussed in the light of a possible activation of mitochondrial PBRs within the adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE.

Acute Disease↗

Immune-induced flavor aversion in mice: modification by neonatal capsaicin treatment.

OBJECTIVE: This study was designed to evaluate the role of c-sensitive fibers in the establishment of immune-induced flavor aversion in mice. METHODS: Mice were treated neonatally with capsaicin in order to destroy c-sensitive fibers; after such treatment, adult animals, immunized or not with ovalbumin, were submitted to a two-bottle preference test, with a choice between water and a sweetened egg white solution. RESULTS: Neonatal capsaicin treatment was unsuccessful in preventing the development of immune-induced aversion to the sweetened solution containing the antigen. Nonetheless, amongst immunized mice, those which had been previously treated with capsaicin showed a significant increment in the preference for the sweetened egg white solution. Furthermore, our data showed that neonatal capsaicin treatment did not interfere with either IgG1 or IgE production. CONCLUSION: The present results suggest that c-sensitive fibers have a role in the transmission of the signals generated by this immune response to the central nervous system, thus contributing to the development of a flavor aversion in mice.

Animals↗

Glue solvent inhalation impairs host resistance to Mycobacterium bovis-induced infection in hamsters.

Industrial organic solvents present in glue are among the common used psychotropic drugs in Brazil and perhaps worldwide; but few data are available concerning the toxic effects of glue sniffing, with almost no information about immunotoxicity. This seems interesting because several drugs and environmental chemicals are recognized as potential immunotoxicants. The present study investigated the effects of forced inhalation of a toluene/n-hexane 1:1 mixture on hamster resistance to Mycobacterium bovis. Adult hamsters were divided at random into 3 equal groups. Animals of Groups E and E inhaled the mixture of toluene/n-hexane twice daily for 37 d. Group C was placed for the same period of time in identical chambers free of solvents. Two days after the beginning of the experiment, Groups E and C were injected ip with 0.5 ml of an activated suspension of M. bovis; Group E received the same volume of a control solution. Hamsters inhaling the toluene/n-hexane mixture (E) exhibited increased weight loss, increased scores of M. bovis colony forming units isolated from liver, lung and spleen, increased granulomatous areas in the liver, lung and spleen. Inhalation of the toluene/n-hexane mixture for 37 d also increased serum cortisol compared to control hamsters. Tuberculosis is an infection with an intracellular bacterium in which sensitivity is determined mainly by host response. The present data demonstrated impaired defense against M. bovis in hamsters inhaling a toluene/n-hexane mixture for 37 d. Since macrophages are the architectural and functional units of the granulomas in tuberculosis, and no data were found about glue solvent effects on cellular immunity, the present data suggest an indirect effect of glue solvents on macrophage/lymphocyte activity via stress induction and central nervous system stimulation of hormonal (ACTH/cortisol) secretion and/or autonomic nervous system activity.

Animals↗

Pavlovian conditioning of lung anaphylactic response in rats.

The present experiment was undertaken to verify if it is possible to impose Pavlovian conditioning on a lung anaphylactic response (LAR) in rats. Two experiments were done. In the 1st, egg albumin (OVA) aerosol inhalation, which induces signs and symptoms of LAR in OVA- sensitized rats, was paired with an audiovisual cue (conditional stimulus, CS). After reexposure to the CS, the signs and symptoms of LAR were quantitatively measured using a scoring system specially developed for this evaluation; the levels of stress response and anxiety were also quantified. Results showed that the rats reexposed to CS only, displayed LAR scores not significantly different from those reexposed to both CS and the antigen; animals of these groups showed significantly higher LAR scores than rats that received no OVA aerosol challenge. High levels of stress and anxiety were observed 30-40 min after the challenge with OVA aerosol. In the 2nd experiment, rats sensitized with OVA and submitted or not to Pavlovian conditioning were observed in the open-field and in the plus maze apparatus in the absence of OVA aerosol but in the presence of the CS; after behavioral observations the animals were sacrificed for serum corticosterone level determination. Both behavioral and biochemical data showed high levels of stress and anxiety in rats for which the antigen was previously paired with the CS; these changes were not observed in animals which received the antigen 24 h after the presentation of the CS (unpaired) or in those exposed to PBS aerosol (the OVA vehicle) only. The present data show not only that LAR can be submitted to Pavlovian conditioning, but also and importantly, that high levels of stress and anxiety are related to the course of LAR.

Administration, Inhalation↗

Effects of treatment with amphetamine and diazepam on Mycobacterium bovis-induced infection in hamsters.

Tuberculosis is an example of an infection with an intracellular bacterium in which sensitivity is determined mainly by the host response. Macrophages are the architectural and functional units of the granulomas described in tuberculosis. Treatment with amphetamine (AMPH) and diazepam has been reported to decrease macrophage activity. The present experiment was undertaken to investigate the effects of AMPH and/or diazepam given alone or in combination on hamster resistance to Mycobacterium bovis. The effects of these treatments on serum cortisol levels were also studied. Adult hamsters were treated i.p. with AMPH (group E1 = 1.0 or 2.0 mg/kg/day), with AMPH (group E2 = 1.0 or 2.0 mg/kg/day) plus diazepam (2.0 mg/kg/day), with diazepam (group E3 = 2.0 mg/kg/day), or with control vehicles (1.0 ml/kg/day) for 40 days. Six days after the beginning of the treatments, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with AMPH plus diazepam exhibited: 1) increased weight loss; 2) increased mortality; 3) increased scores of M. bovis colony forming units (CFU) isolated from liver, lung and spleen; 4) increased granuloma areas measured in the liver, lung and spleen. These effects were not induced by AMPH (1.0 or 2.0 mg/kg/day) given alone and were produced by diazepam (2.0 mg/kg/day) treatment per se. Furthermore, AMPH (2.0 mg/kg/day) and diazepam (2.0 mg/kg/day) given alone or in combination for 20 days increased the serum levels of cortisol in relation to control hamsters, with the effect being higher in the animals treated with both drugs. The present data, which demonstrate an impaired defense against M. bovis in hamsters treated with AMPH plus diazepam or with diazepam alone, were tentatively explained on the basis of a direct and/or indirect action of the drugs on macrophage/lymphocyte activity. In the former case, the effects may be related to stimulation of peripheral benzodiazepine receptor sites (PBR) present on macrophages/lymphocytes and/or to a direct effect of ACTH on immune cells, while in the latter they may be mediated by cortisol via PBR and ACTH stimulation of the adrenals.

Amphetamine↗

Diazepam effects of peritoneal macrophage activity and corticosterone serum levels in Balb/C mice.

In the present experiment we investigate the effects of diazepam on macrophage activity and serum corticosterone levels in mice. Adult mice were treated with diazepam (1.5 mg/kg/day - group E) or with control solution (group C1) for 7 days; some animals were only handled, receiving no treatment (group C2). Oral onco-BCG was used for peritoneal macrophage activation. Diazepam treatment: 1-decreased macrophage spreading and phagocytosis; 2-decreased the concentrations of H2O2 spontaneously but not phorbol myristate-acetate-induced release. In relation to mice of group C1, diazepam treatment increased the serum levels of corticosterone. No differences were detected between data of groups C1 and C2 both for macrophage activity and serum corticosterone levels. The present data were explained on the basis of a synergistically action for diazepam through peripheral type binding sites (PBR) present in both adrenals and macrophages, stimulating adrenal glucocorticoid production and altering the macrophage cytokine network.

Administration, Oral↗

Effects of prenatal diazepam treatment on Mycobacterium bovis-induced infection in hamsters.

In utero exposure of rats to low dosages of diazepam has been found to result in depression of cellular and humoral immune responses during adulthood, with marked changes in macrophage spreading and phagocytosis. The present experiment was undertaken to investigate the resistance of adult hamsters to Mycobacterium bovis after prenatal exposure to diazepam. Time-pregnant hamsters were exposed to diazepam (1.0 or 1.5 mg kg(-1) day(-1) subcutaneously) or vehicle from gestational day 9 to 15. A total of 36 different litters (12 of them control and 12 for each experimental group) born after a 16/17-day gestation were used. One male from each litter was infected twice with identical inoculum concentrations of M. bovis at 75 and 107 days of age. This infection model involves the participation of macrophages and T and B cell populations. The animals prenatally exposed to the higher (1.5 mg/kg) dose of diazepam exhibited: (1) increased weight loss, (2) increased mortality, (3) increased granuloma areas measured in the liver, lung and spleen, (4) increased spleen weight, and (5) increased scores of M. bovis colony forming units (CFU) isolated from liver, lung and spleen. These effects were dose-dependent, and were not detected or were less severe in animals treated with the lower (1.0 mg/kg) dose of diazepam as well as in those of the control group. The present data demonstrate an impaired defence against M. bovis in adult hamsters after in utero exposure to a dosage of 1.5 mg/kg of diazepam.

Animals↗

Kinetic analysis of GM1 effects on haloperidol-induced dopaminergic supersensitivity.

The relative affinity of metoclopramide as indicated by K(B) values was calculated in control and in haloperidol-withdrawn rats treated or not with monosialoganglioside-1 (GM1) by using dose-response curves constructed for apomorphine-induced stereotyped behavior. Haloperidol withdrawal decreased K(B) data--that is, increased the D2-receptor affinity for metoclopramide. GM1 treatment per se did not modify K(B) values but, when given in combination with haloperidol, GM1 induced a decrease in K(B) values. No differences were found in K(B) data when GM1 was administered after withdrawal from haloperidol.

Animals↗