Rat system

The comparison of fish bioassays (6) with the calculated effective doses indicate that the two most potent brevetoxins, PbTx-1 and PbTx-7, also are most effective at displacing tritiated probe from its specific site of action. The considerably lower potency of brevetoxins PbTx-5 and PbTx-6 in the rat system suggest that these two toxins may bind with lesser affinity to site 5. In a general sense, this is indicated in Table II, and is summmarized in Table III. 

Barbier et al. (2004) investigated the effects of a highly selective and novel non-imidazole H3 receptor antagonist, 1, l-[4-(3-piperidin-l-yl-propoxy)-benzyl]-piperidine (JNJ-5207852), on sleep and wakefulness in mice and rats. Systemic injections of JNJ-5207852 (1-10 mg/kg, s.c.) increased the time spent in wakefulness with a concomitant decrease in NREM and REM sleep in both mice and rats. The overall increase in wakefulness was due to an increase in the number of wakefulness bouts. Spectral analysis of the EEG also revealed a reduction in total delta power following systemic injections of this compound (Barbier et ah, 2004). 

More recently, the action of subtype-selective 5-HT2 receptor antagonists on sleep variables was assessed in the rat. Systemic administration of the 5-HT2a... 

Nicotine is an addictive substance with rewarding and reinforcing properties. On the other hand, the autonomic responses following an acute nicotine treatment and the bitter taste of nicotine may cause aversion. This aversion may impact conditioned effects to nicotme. Rinker et al. (2008) studied possible sex differences in taste aversion mduced by nicotine in rats systemic nicotine or saline injections were paired wim oral saccharine. Although nicotme did produce a weak taste aversion, no sex differences were observed, excluding the possible contribution of the aversive properties of nicotine on sexually dimorphic responses to nicotine. The authors conclude that sex differences may arise from differences in the rewardmg properties of the drug. 

Wade, M.G., W.G. Foster, E.V. Younglai, et al. 2002. Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats Systemic, immune, and reproductive effects. Toxicol. Sci. 67 131-143. 

Toxicological studies have suggested that the species specificity for induction of ovarian tumors (produced in mice but not rats) occurs because the blood level of the ovotoxic VCH metabolite VCH-1,2-epoxide is dramatically higher in VCH-treated female mice compared with rats. VCH has been shown to be metabolized by the liver of mice to the ovotoxic metabolite (VCH-1,2-epoxide), which circulates in blood and is delivered to the ovary, where it destroys small oocytes. This destruction of small oocytes is considered to be an early event in carcinogenesis. Species difference in epoxidation of VCH by hepatic micro-somes correlates well with the differences observed in the blood concentration of VCH-1,2-epoxide and VCH ovarian toxicity. Further in vitro studies have found that the rate of VCH epoxidation in humans by human hepatic microsomes was 13- and 2-fold lower than epoxidation by mouse and rat systems respec-tively. Therefore, if the rate of hepatic VCH epoxidation is the main factor that determines the ovotoxicity of VCH, rats may be a more appropriate animal model for humans. 

Goth, R. and Rajewsky, M.F. (1974). Persistence of 6-ethylguanine in rat system specific carcinogenesis by ethylnitrosourea, Proc. NatL Acad. Sci. 71,639. 

The metabolic activation of chemicals varies substantially within and among species, including man. Theoretically, a human activation system would be more suitable than a rat system for estimating human risk. However, that is not practical, and more research is needed to find a system that leads to the best human predictions. 

The effects of cerebral injections of methamphetamine on striatal TPH activity were also investigated (figure 1). In an anesthetized rat, systemically administered methamphetamine (10 mg/kg) decreased striatal TPH activity. However, bilateral injections of methamphetamine into the neostriatum (100 g) failed to decrease striatal TPH activity 3 hours after treatment. To determine whether multiple areas of the brain are involved in methamphetamine-induced changes in striatal TPH, microinjections of methamphetamine were administered into the substantia nigra or lateral midbrain and into the striatum. Three hours after treatment, injections of methamphetamine into the striatum (100 g) and the substantia nigra (25 g) or the lateral midbrain (area of B9 serotonergic cell bodies) (50 g) did not reduce TPH activity in the neostriatum. 

Systolic arterial blood pressure Spontaneously hypertensive rats Systemic lupus erythematosus Society of Toxicology Torsades de pointes... 

In human keratinocytes, P450 24A1 luRNA was also elevated by la,25-dihydroxyvitaminD3 [2444]. Studies with rat systems indicate that this response is also mediated by VDR response elements and that two of these (VDRE-l, VDRE-2) operate synergistically [2452]. Afimctional Ras-... 

Several recent studies have demonstrated the potential of cadmium to cause prostate cancer in rats. Systemic cadmium exposure, including oral exposure, results in adenomas of the rat prostate (Waalkes et al. 1988a, 1989 Waalkes and Rehm 1992). It appears that normal testicular function, i.e., androgen production, is requisite for development of cadmium-induced prostatic tumors. 

Kita Y, Li XK, Ohba M, FuneshimaN, Enosawa S, Tamuia A Suzuki K, AmemiyaH Hayashi S, Kazui T, Suzuki S. Prolonged cardiac allograft survival in rats systemically injected with adenoviral vectors containing CTLA4Ig-gene. Transplantation 1999 68 758-766. 

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