I. N. Orlova

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.

Experimental Model of Combined Pain and Depression Status in Rats

Combined pain and depression status in rats was created by inducing experimental depressive syndrome (by subchronic injection of MPTP proneurotoxin) in animals with manifest and developing neurogenic pain syndrome induced by preliminary crossing of the sciatic nerve in the hind limb. The neurogenic pain syndrome augmented by some parameters the depressive symptoms and provoked manifestation of signs of depressive behavior in animals treated with saline.

Effect of a Prolyl Endopeptidase Inhibitor Benzyloxycarbonyl-Alanyl-Proline on the Development of Experimental Depressive Syndrome in Rats

The effects of a competitive prolyl endopeptidase inhibitor benzyloxycarbonyl-alanylproline were studied in rats with experimental dopamine deficiency-dependent depressive syndrome due to systemic administration of a proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine for 14 days. The inhibitor was injected intraperitoneally 30 min before treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2nd week of the study). This substance contributed to rapid disappearance of depressive symptoms during the recovery of behavioral activity. Our results indicate that benzyloxycarbonylalanyl-proline has the antidepressant properties.

Activities of prolyl endopeptidase and dipeptidyl peptidase IV in brain structures of rats with dopamine deficiency-dependent MPTP-induced depressive syndrome.

The development of MPTP-induced depressive syndrome in rats was accompanied by activation of prolyl endopeptidase and dipeptidyl peptidase IV in the brain frontal cortex. Prolyl endopeptidase activity in the striatum also increased under these conditions. Our results indicate that proline-specific peptidases in the target structures of the brain dopaminergic system are involved in the pathogenesis of dopamine deficiency-dependent depressive states.

Experimental depressive-pain syndrome in rats with initial various anxiety-phobic levels: a behavioral study.

Modeling of neurogenic pain syndrome by sciatic nerve transection in rats with pronounced dopamine-deficiency-dependent 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-induced experimental depressive syndrome forms a stable state of combined pain and depression, which can be considered as a model of the pain-depressive syndrome. The neurogenic pain syndrome prolongs the state of behavioral depression in rats irrespective of their initial anxiety level. The depressive symptoms can potentiate the severity of pain syndrome. By a number of indices, more pronounced behavioral changes during the development of pain-depressive syndrome occur in initially nonanxious rats.

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.

Effect of Prolyl Endopeptidase Inhibitor Benzyloxycarbonyl-Methionyl-2(S)-Cyanopyrrolidine on the Course of Experimental Depressive Syndrome in Rats

The effects of noncompetitive prolyl endopeptidase inhibitor benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine were studied in rats with the experimental dopamine deficiency-dependent depressive syndrome induced by systemic injections of a pre-neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin for 14 days. The inhibitor (3.0 mg/kg, i.p., 30 min before pre-neurotoxin injection on days 8-14) alleviated depression symptoms and promoted normalization of behavioral activity after drug withdrawal. The obtained data reflected therapeutic antidepressant properties of inhibitor for prolyl endopeptidase benzyloxycarbonyl-methionyl-2(S)-cyanopyrrolidine.

Involvement of brain dopaminergic systems in the development of an MPTP-induced depressive state in rats.

A depressive state was induced in Wistar rats by repeated i.p. injections of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces the death of dopaminergic neurons in the brain. Signs of the development of the experimental depressive state were a reduction in body weight and an increase in the proportion of REM sleep during daytime sleep. The rearrangement of the spectral characteristics of electrical activity during the development of experimental depressive syndrome in rats was shown to occur in target structures of the nigrostriatal, mesocortical, and mesolimbic dopaminergic systems of the brain, as well as in the amygdala and hippocampus. The most marked changes were seen in the terminal field of the nigrostriatal dopaminergic system and hippocampus. Spectral rearrangements of electrical activity in the theta-1 and theta-2 ranges in the hippocampus and dopaminergic structures suggest the involvement of the hippocampus in mediating changes in the emotional status of the experimental animals during the development of the MPTP-induced depressive state.

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.

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.