Portal-systemic shunting and the disruption of circadian locomotor activity in the rat

Coy, Dale L.; Mehta, Rajeev; Zee, Phyllis C.; Salchli, Fred; Turek, Fred W.; Blei, Andrés T.

doi:10.1016/0016-5085(92)91116-l

Cited by 34 publications

(24 citation statements)

References 14 publications

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“…Among these abnormalities are the significantly reduced spontaneous locomotor activity and exploration, 3 as well as the reduced or completely abolished differences between day time and night time activity, suggesting a disruption of their circadian rhythmicity. [4][5][6][7][8][9][10] These rats also have disturbances in their food intake 11 and show marked growth retardation. 12 Although much research has been performed to elucidate the pathophysiological background of PSE, the exact mechanisms that underlie this condition are still largely unclear.…”

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confidence: 99%

Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

et al. 2000

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To find out whether the changes in the brain histaminergic system are involved in the pathophysiology of portalsystemic encephalopathy, we examined the effects of histamine H 1 receptor blockade on spontaneous locomotor activity, feeding, and circadian rhythmicity in rats with portacaval anastomosis (PCA). Pyrilamine, an H 1 receptor blocker (15 mg/kg/day), was delivered with osmotic minipumps. Spontaneous locomotor activity was recorded for 72 hours in the open-field with an electromagnetic detector. Food intake was monitored twice daily at the end of the light (7 PM) and the dark (7 AM) phases for 3 days. Histamine H 1 receptor density in the suprachiasmatic nucleus (SCN) was examined with receptor autoradiography, employing [ 3 H]pyrilamine. PCA surgery led to decreased movement time and velocity and flattened amplitude of the circadian rhythms of locomotion and feeding. In sham-operated rats, pyrilamine significantly decreased the movement time and velocity, as well as the total food consumption and completely abolished the circadian rhythmicity of locomotion. In contrast, pyrilamine increased the movement time and velocity in PCA-operated rats, particularly in the dark phase, and improved the precision of the circadian rhythms of locomotion and feeding. Histamine H 1 receptor density was not altered by PCA surgery, whereas pyrilamine treatment led to the complete blockade of H 1 receptors in both sham-and PCA-operated rats. We suggest that histaminergic imbalance has contributed to the generation and maintenance of the decreased spontaneous locomotor activity and altered circadian rhythmicity following PCA surgery in the rat, probably via an H 1 receptor-mediated mechanism. (HEPATOL-OGY 2000;31:336-344.)Animal models of human disease provide the means of studying the pathological condition in a way that is not always possible in human patients. The rat with an end-toside portacaval anastomosis (PCA) represents an attractive model of portal-systemic encephalopathy (PSE) 1,2 because many of the behavioral abnormalities that occur in this model correspond to the subclinical forms of PSE. Among these abnormalities are the significantly reduced spontaneous locomotor activity and exploration, 3 as well as the reduced or completely abolished differences between day time and night time activity, suggesting a disruption of their circadian rhythmicity. 4-10 These rats also have disturbances in their food intake 11 and show marked growth retardation. 12 Although much research has been performed to elucidate the pathophysiological background of PSE, the exact mechanisms that underlie this condition are still largely unclear. PSE has been described as a disorder of multiple neurotransmitter systems. 13 Specifically, the histaminergic synaptic imbalance, which becomes apparent shortly 14,15 and persists for at least 8 months after surgery, 12,16-18 is among the most interesting consequences of portacaval shunting in the rat.We have previously shown that rats with PCA have profound disturbances in their brain histaminergi...

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Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

et al. 2000

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“…Moreover, it was found that these changes were reversible by applying to the animal effective treatment for HE and, as mentioned before, the model can be relevant for studying the HE. Specifically, Conjeevaram and co-workers (18) demonstrated that by adding neomycin to drinking water to rats with PCS the motor activity was reduced after exposing them to a new and dark environment, while Coy and colleagues also did so using a more sophisticated technique by measuring disturbances of the circadian motor activity (19). This group also demonstrated that operated rats shown the same improvement when they were subjected to low protein diet.…”

Section: Portocaval Shunt In Ratsmentioning

confidence: 99%

“…Several authors have detailed some reflex tests and evaluating responses to stimuli (26), difficult to interpret, or computerized activity measurements (13,14) or circadian rhythms (19), which represent a forward step in this sense. According to Mullen (27), rats subjected to PCS have an uncertain response of the spontaneous motor activity, so even doing an adequate shunt; a large number of animals is required to demonstrate significant behavioral changes in operated animals compared to controls, despite the use of more sophisticated methods of measurement.…”

Section: Portocaval Shunt In Ratsmentioning

confidence: 99%

Experimental models for hepatic encephalopathy

Díaz-Gómez¹,

Jover²,

delCampo³

et al. 2011

Rev. esp. enferm. dig.

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INTRODUCTIONAlthough there are many models for animal testing, the ideal model for chronic liver disease involving hepatic encephalopathy has not been described yet. Different problems associated with the models have led researchers to develop their own, sometimes unique experimental models, which makes difficult the comparison between the results of the conducted studies (1). Hepatic encephalopathy (HE) definition, nomenclature, diagnosis and quantification consensus were published in 2002 (2) where three types of HE were considered: type A, associated with acute liver failure, type B, associated with the existence of porto-systemic communication (by-pass) without intrinsic liver disease and type C, associated to liver cirrhosis. HE type C, in turn, is classified according to their form of presentation as spontaneous or episodic HE, in relation to precipitating factors, persistent HE is subdivided into mild (HE grade I), severe (HE II-IV) or treatment-dependent (early developed after abolition of treatment) and finally, the minimal HE, as the first manifestation of HE. HE type C is the most common form and from a clinical point of view, the episodic HE type because of liver cirrhosis decompensation is the most typical and relevant.

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“…On an experimental level, a series of models that reproduces both types of hepatic encephalopathy has been developed (Blei et al 1992). Among the models that reproduce acute hepatic failure are those that involve an exclusion of the hepatic function (hepatectomy or devascularization of the liver) or those that use hepatotoxins, such as D-galactosamine or thioacetamide.…”

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Portacaval shunt control animals: physiological consequences derived from the sham operation

et al. 1997

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SummaryThe portacaval shunt in the rat is a frequently used experimental model of porto systemic encephalopathy. Among other consequences of this surgical preparation is an important decrease in hepatic and testicular volume. Different sham-operation methods including a laparotomy were used as controls in each case. Given that the liver volume varies greatly in comparison to body weight in the sham-operated animals, this paper aims to evaluate the possible consequences of the sham operation. It concludes that control animals without manipulation, in addition to the respective controls of portacaval shunt, should be used in every case.

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Portal-systemic shunting and the disruption of circadian locomotor activity in the rat

Cited by 34 publications

References 14 publications

Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Experimental models for hepatic encephalopathy

Portacaval shunt control animals: physiological consequences derived from the sham operation

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Portal-systemic shunting and the disruption of circadian locomotor activity in the rat

Cited by 34 publications

References 14 publications

Effects of the histamine H1receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Effects of the histamine H1receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Experimental models for hepatic encephalopathy

Portacaval shunt control animals: physiological consequences derived from the sham operation

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Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis

Effects of the histamine H₁receptor blocker, pyrilamine, on spontaneous locomotor activity of rats with long-term portacaval anastomosis