Effect of melipramine on the development of experimental depressive syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The effects of chronic administration of melipramine on the development of behavioral signs of depression in rats are studied using the model of a depressive syndrome induced by systemic administration of MPTP. Preadministration of melipramine prevents such MPTP-induced behavioral signs of depression in rats as decreased motor activity, reduced total daily liquid intake, reduced preference of sucrose solution over water, and increased depression index. Translated fromByulleten' Eksperimental'noi Giologii i Meditsiny, Vol. 120, N ^o . 8, pp. 160–163, August, 1995     

A new model of the depressive syndrome induced by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats

Animals treated with MPTP neurotoxin displayed lowered motor and exploratory activity in the open field test, reduced daily intake of water with a preference for sugar solution over water, prolonged immobilization, and increased index of depression in the forced swimming test. The changes in rat behavior were preserved for at least a week after withdrawal of the drug. The data attest to the development of a state of lowered motivational activity combined with ahedony and “behavioral despair” in response to MPTP, making it possible to consider this state as a new experimental model of dopamine-dependent depressive syndrome in rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 125–128, February, 1995     

Effect of parlodel on the development of a depressive syndrome induced by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats

Effects caused by the chronic administration of Parlodel on the development of behavioral signs of depression in rats are studied using the new model of depressive syndrome induced by the systemic administration of MPTP. Pretreatment with Parlodel prevents locomotor depression, weight loss, reduction of liquid intake, a decline of the preference of sucrose solution over water, and a rise of the depression index and promotes a quicker restoration of exploratory activity, i.e., it safeguards rats from manifestating the behavioral signs of MPTP-induced depression. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 7, pp. 66–70, July, 1995     

Disturbances in humoral and cell-mediated immunity in rats with experimental depressive syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6—tetrahydropyridine

Changes in humoral and cell-mediated immunity are studied in rats with 1-methyl-4-phenyl-1,2,3,6—tetrahydropyridine (MPTP)-induced depressive syndrome. A decrease in the lymphocyte count and in absolute and relative T cell counts and absolute B cell counts in peripheral blood and an increase in serum concentration of circulating immune complexes (CIC) are demonstrated. Serum CIC content increases, while the relative count of peripheral blood T cells remains decreased two weeks after discontinuation of MPTP and normalization of rats' behavior. Serum CIC content decreases and T cell count normalizes one month after discontinuation of MPTP. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 308–311, March, 1997     

REM sleep disorders in rats with experimental depressive syndrome caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Rats receiving daily injections of the neurotoxin MPTP in a dose of 20 mg/kg for 12 days develop disorders of REM sleep, including increased frequency of REM-sleep episodes, decreased REM latency, and increased REM sleep duration, both absolute and relative. The first two of these REM sleep disorders are characteristic of endogenous depression. The results indicate that systemically administered MPTP causes a state similar to endogenous depression. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 2, pp. 138–142, February, 1997     

Effect of interferon on the development of parkinsonism induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl/6 mice

The administration of reaferon, a recombinant α-interferon preparation, hampers the development of parkinsonism caused by MPTP administration in C57Bl/6 mice. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 503–505, May, 1996     

Count and phagocytic activity of leukocytes in rats with experimental depressive syndrome caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Leukocyte count decreased, relative content of neutrophils and monocytes increased, and their phagocytic activity was suppressed in rats with 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced depressive syndrome at the stage of acute behavioral depression. The severity of behavioral depression inversely correlated with changes in the absolute neutrophil and monocyte counts.     

Lymphocytes from mice with a 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine(MPTP)-induced parkinsonian syndrome reduce motor activity in C57Bl/6 mice

Motor activity of C57Bl/6 mice is found to be decreased following syngeneic transfer to them of splenocytes from mice with an MPTP-induced parkinsonian syndrome. The decrease in motor activity does not result from the transfer of MPTP and is apparently associated with the transfer of B lymphocytes and with antibody production by these cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 232–234, March, 1994     

Count and phagocytic activity of leukocytes in rats with experimental depressive syndrome caused by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Leukocyte count decreased, relative content of neutrophils and monocytes increased, and their phagocytic activity was suppressed in rats with 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine-induced depressive syndrome at the stage of acute behavioral depression. The severity of behavioral depression inversely correlated with changes in the absolute neutrophil and monocyte counts.     

Experimental parkinsonian syndrome induced in rats by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR. Laboratory of Synthesis of Active Compounds and Laboratory of Psychopharmacology, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 4, pp. 397–401, April, 1988.     

The clinical syndrome of striatal dopamine deficiency. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a syndrome that resembles Parkinson's disease. To compare the biochemical abnormalities produced by this compound in human beings with those occurring in Parkinson's disease, we examined biogenic amine metabolites in cerebrospinal fluid and urine from six patients with MPTP-induced parkinsonism and eight patients with Parkinson's disease. In both forms of parkinsonism, the cerebrospinal fluid levels of homovanillic acid, the major metabolite of dopamine, were reduced, whereas the levels of the serotonin metabolite 5-hydroxyindoleacetic acid were normal. The cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the major metabolite of norepinephrine in the brain, after adjustment for plasma MHPG, were elevated (greater than 6.0 ng per milliliter) in MPTP-induced parkinsonism, whereas MHPG levels were reduced (less than 6.0) in Parkinson's disease. Neurons containing norepinephrine in the brain are involved in the degenerative process of Parkinson's disease, whereas they are spared in MPTP-induced parkinsonism. The selective destruction by MPTP of nigrostriatal dopamine neurons that is responsible for the movement disorder also appears to result in an increase in central noradrenergic activity, which is not possible in Parkinson's disease. Thus, differences in central noradrenergic activity, reflected in cerebrospinal fluid levels of MHPG, distinguish these two forms of parkinsonism.     

Electrical activity in the structures of the caudate-putamen complex in experimental depressive syndrome

Electrical activity of rat brain was modified by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administered according to a scheme inducing experimental depressive syndrome. The changes were manifested by local epileptiform activity in the structures of the caudate-putamen complex, an increase in the δ-rhythm power, and a decrease in the α-rhythm power, which attests to hyperactivity in these structures. An increase in the δ-rhythm power was observed in the hippocamp. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 266–269, September, 1998     

Effect of parlodel on brain electrical activity in experimental depressive syndrome in rats

In rats with experimental MPTP-induced depressive syndrome, chronic administration of parlodel prevented epileptiform activity, an increase in δ-band and a decrease in α-band spectral powers in the caudate-putamen structures, and an increase in δ-band spectral power in the hippocampus. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 152–155, February, 2000     

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on ultrastructure of nigral neuromelanin in Macaca fascicularis

In neurons of the substantia nigra (SN) of Macaca fascicularis the administration of parkinsongenic doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused morphological changes of the neuromelanic granules. Under light microscopy, the granules appeared more dispersed and larger. Electron microscopy revealed coalescence of granules in large masses with loss of the electrodense component. Phagocytosis of neuromelanin by glial cells was also observed. In several neurons the neuromelanic changes were evident in the presence of morphologically intact mitochondria. These data suggest an interaction between MPTP and neuromelanin that may have relevance to the nigrotropic toxicity of MPTP and are in agreement with observations on neuromelanin in parkinsonian patients.     

Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

BACKGROUND. Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism. METHODS. We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation. RESULTS. Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications. CONCLUSIONS. Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.     

Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content

We examined both in vitro tyrosine hydroxylase (TH) activity and TH content determined by a new enzyme immunoassay in the mouse striatum after repeated systemic injection of MPTP. Repeated systemic administration of MPTP to mice (30 mg/kg per day, subcutaneously for 8 days) caused an approximately 65% decrease of both TH activity and TH content in the striatum. The intensity of immunohistochemical staining of TH protein in the striatum was also reduced in MPTP-treated mice. These results indicate that the reduction of TH activity in vitro after the repeated administration of MPTP is due to reduction of TH protein as a result of nerve degeneration.     

Effects of Parlodel on sleep-wake cycles in rats with MPTP-induced depressive syndrome

Chronic treatment with Parlodel normalized the parameters of REM sleep disturbed by multiple systemic administration of the dopaminergic neurotoxin MPTP, which is a novel model of depressive syndrome in rats. When administered prior to MPTP, Parlodel reduced the occurrence of REM sleep episodes, shortened duration of REM sleep, and prolonged REM sleep latency. It also reduced the percentage of REM sleep episodes in the total time of sleep. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 380–383, April, 1999     

Acute ultrastructural and behavioral effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice

Acute actions of MPTP on behavior and on neostriatal ultrastructure were examined in young C57 Black mice. Autonomic, motor, and toxic effects of MPTP exhibited dependence on dose (20-40 mg/kg) and time during the first 4 h after subcutaneous injection. The ultrastructure of the neostriatum was altered very quickly (2-24 h) after single injections of MPTP. Darkened glial processes were found within 2-8 h, followed by dark degeneration of synaptic boutons, especially those making small symmetric synapses. More rarely, swollen axons and postsynaptic degeneration were also observed.     

Bladder hyperreflexia induced in marmosets by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

In marmosets, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes degeneration of the cell bodies of the substantia nigra and the animals subsequently develop parkinsonian symptoms. Cystometrograms obtained from such animals while under pentobarbitone anaesthesia, showed their bladders to be hyperreflexic when compared to those of normal animals of the same age (less than 2 years). Bladder hyperreflexia is present in many parkinsonian patients and is difficult to treat, partly because it is made worse by dopaminergic agents. This is the first demonstration of an effect of MPTP on this type of peripheral function. It suggests the suitability of MPTP-treated marmosets for studying the mechanisms by which a loss of nigrostriatal dopamine leads to bladder hyperreflexia and for devising pharmacological strategies which may be of therapeutic value in the clinic.