Histamine- and haloperidol-induced catalepsy in aged mice: differential responsiveness to l-DOPA

Ionov, Ilya D.; Severtsev, Nicholas N.

doi:10.1007/s00213-012-2706-0

Cited by 12 publications

(13 citation statements)

References 27 publications

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“…Since the mean lifespan for these animals was approximately 750 days (12), these animals were considered as young and old. Rats were housed as described previously (13). Animals were randomly divided into groups of seven animals.…”

Section: Animalsmentioning

confidence: 99%

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Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

Ionov¹,

Turgeneva²

2015

Avicenna J Neuro Psych Physio

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Background:The decreased level of somatostatin and increased level of histamine are detected in the Parkinsonian brain. In old Wistar rats, the brain somatostatin deficiency can initiate catalepsy that suggests the pathogenic significance of this abnormality in Parkinson's disease (PD). The ability of histamine to affect the somatostatin deficiency action is not studied. Objectives: The current study aimed to examine if histamine alters the cataleptogenic activity of the brain somatostatin deficiency in Wistar rats. Materials and Methods:The animals used in the study were 100 -110 and 736 -767 days old. Catalepsy was evaluated by the bar test. The inhibition of the brain somatostatin activity was simulated by I.C.V. administration of cyclosomatostatin (cycloSOM), a somatostatin receptor antagonist. Results: CycloSOM (0.2, 1.0, and 5.0 µg) and histamine (1.0 and 10.0 µg) alone were ineffective in both young and old animals. In combination, however, cycloSOM and histamine initiated cataleptic response in old rats. Effect of the combination was inhibited by H1 and H2 but not H3 antagonists. Conclusions: CycloSOM and histamine synergistically exert catalepsy in old rats. In light of these data, the combination of the decreased brain level of somatostatin and increased brain level of histamine may be of pathogenic relevance for extrapyramidal signs in PD.

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Section: Animalsmentioning

confidence: 99%

“…CycloSOM at the doses of 0.2, 1.0, 5.0, and 10.0 µg and histamine at the doses of 1.0 and 10.0 µg were administered intracerebroventricularly (i.c.v.). The doses were selected according to the previous studies (8,13).…”

Section: Drugsmentioning

confidence: 99%

Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

Ionov¹,

Turgeneva²

2015

Avicenna J Neuro Psych Physio

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“…For example, Tournissac et al (2016) demonstrated potentiated cold-induced tau phosphorylation in old mice, a mechanism that may contribute to the susceptibility of older populations to develop Alzheimer disease. Nigrostriatal dopaminergic neurons of older mice appeared more sensitive to neurotoxicity (Thiruchelvam et al, 2003) and to histamine-induced cataplexy and less responsive to L-DOPA (Ionov and Severtsev, 2012), which sheds further light on the mechanisms involved in Parkinson’s disease.…”

Section: Introductionmentioning

confidence: 99%

Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

Wolf

Lotan

Lifschytz

et al. 2017

Front. Aging Neurosci.

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Bilateral common carotid artery stenosis (BCAS) models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month) and young adult (3 month) female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014): on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS. However, on the second day of the test, latencies of old BCAS mice were significantly longer than old control mice (p = 0.049), while latencies of old controls were similar to those of the young adult mice, indicating more severe impairment of hippocampal dependent learning and working memory by BCAS in the older mice. Fluorescence staining of myelin basic protein (MBP) showed that old age and BCAS both induced a significant decrease in fluorescence intensity. Evaluation of the number oligodendrocyte precursor cells demonstrated augmented myelin replacement in old BCAS mice (p < 0.05) compared with young adult BCAS and old control mice. While microglia morphology was assessed as normal in young adult control and young adult BCAS mice, microglia of old BCAS mice exhibited striking activation in the area of degraded myelin compared to young adult BCAS (p < 0.01) and old control mice (p < 0.05). These findings show a differentially more severe effect of cerebral hypoperfusion on cognitive function, myelin integrity and inflammatory processes in aged mice. Hypoperfusion may exacerbate degradation initiated by aging, which may induce more severe neuronal and cognitive phenotypes.

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“…In direct experiments, exogenous histamine produced selective degeneration of dopaminergic neurons in rat substantia nigra [24]; in essence, histamine is the only brain factor that is found to induce the main histopathological feature of iPD. Besides, in mice, histamine can exert catalepsy that is antagonized by levodopa [25][26][27]. Alternatively, histamine H 1 receptor antagonists can elevate dopamine levels in rat neostriatum and nucleus accumbens [28]; these drugs also attenuate cataleptic response induced by haloperidol [23,29] and a few other cataleptogens [29].…”

Section: Introductionmentioning

confidence: 99%

Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

Ionov¹,

Gorev²,

Pushinskaya³

2018

Current Topics in Pharmacology

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A decrease in somatostatin level is observed in parkinsonian brain. We recently reported that rats given an intracerebroventricular injection of a somatostatin antagonist, cyclosomatostatin, fall into catalepsy; the effect was observed in aged but not young animals. To evaluate the predictive validity of the cyclosomatostatin-induced catalepsy as a model of extrapyramidal disorders, the sensitivity of this catalepsy to clinically effective antiparkinsonian agents was determined. We examined the effects of levodopa and histamine antagonists; also, given an inverse association between Parkinson's disease and tobacco smoking, nicotine was tested. The experiments were conducted using 27-28month-old male Wistar rats. Catalepsy was measured using the bar test. Cyclosomatostatin-induced catalepsy was strongly antagonized by levodopa, which indicates a role for central dopaminergic deficiency in this model. Similarly, histamine H 1receptor antagonist, diphenhydramine, exhibited anticataleptic activity; in contrast, antagonists at H 2and H 3-receptors were without effect. Cataleptic response was inhibited by nicotine; the nicotine sensitivity distinguishes this catalepsy from other models, in particular, from haloperidol-induced catalepsy. Diphenhydramine and nicotine alone only partly suppressed catalepsy; however, coadministration of these drugs almost totally reversed the cataleptogenic effect of cyclosomatostatin. Thus, a similarity between the cyclosomatostatininduced catalepsy and Parkinson's disease with regard to the sensitivity to anti-parkinsonian agents was found. This supports the validity of the model as well as the role of somatostatinergic deficiency in the mechanism of parkinsonian symptoms. Coadministration of diphenhydramine and nicotine appears to be a promising treatment for extrapyramidal disorders in Parkinson's disease.

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Histamine- and haloperidol-induced catalepsy in aged mice: differential responsiveness to l-DOPA

Abstract: The mouse histamine-induced catalepsy, unlike haloperidol-induced one, displays the same pattern of age dependency as PD. These findings support an involvement of histamine in the PD pathogenesis.

Cited by 12 publications

References 27 publications

Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

Histamine Potentiates Cyclosomatostatin-Induced Catalepsy in Old Rats

Differentially Severe Cognitive Effects of Compromised Cerebral Blood Flow in Aged Mice: Association with Myelin Degradation and Microglia Activation

Cyclosomatostatin-induced catalepsy in the aged rat: a response to levodopa, diphenhydramine and nicotine

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