Mice, Inbred DBA

OBJECTIVE: Chebulagic acid (CHE) from the immature seeds of Terminalia chebula was identified from a natural product library as a potent suppressor of T cell activity. This study examined the effectiveness of CHE against the onset and progression of collagen-induced arthritis (CIA) in mice. METHODS: Arthritis was induced in DBA/1J mice by subcutaneous immunization with bovine type II collagen on days 0 and 21. CHE was administered intraperitoneally for 3 weeks, either as prophylaxis (10 or 20 mg/kg) before disease onset or as therapy (20 mg/kg) after disease onset.

Rheumatoid arthritis is a chronic degenerative autoimmune disease characterized by persistent inflammation of synovial membranes, which leads to cartilage destruction and bone erosion. To date, there are no effective therapies to slow the progress of this degenerative condition. Here, we evaluate the anti-arthritic effect of chebulanin, an abundant anti-inflammatory agent isolated from Terminalia chebula, in collagen induced arthritis in DBA/1 mice by intragastric administration.

Many degenerative diseases that occur with aging, as well as premature aging syndromes, are characterized by presenting cells with critically short telomeres. Telomerase reintroduction is envisioned as a putative therapy for diseases characterized by telomere exhaustion. K5-mTert transgenic mice overexpress telomerase in a wide spectrum of tissues. These mice have a higher incidence of both induced and spontaneous tumors, resulting in increased mortality during the first year of life.

Xenobiotic metabolism has been proposed to play a role in modulating the rate of aging. Xenobiotic metabolizing enzymes (XME) are expressed at higher levels in calorically restricted mice (CR) and in GH/IGF-I-deficient, long-lived mutant mice. In this study, we show that many phase I XME genes are similarly upregulated in additional long-lived mouse models, including "crowded litter" (CL) mice, whose lifespan has been increased by food restriction limited to the first 3 wk of life, and in mice treated with rapamycin.

The effects of naltrexone on the increase in locomotor activity induced by a low dose (1.35 g/kg IP) of ethanol and on the duration of loss of righting reflex after a high dose (3.5 g/kg) of ethanol were studied in BALB/c, DBA/2, and C57BL/6 mice. Ethanol increased locomotor activity in DBA and BALB mice, but not in C57BL mice. Naltrexone, at a dose of 0.1 mg/kg, antagonized the ethanol-induced increase in locomotion similarly in DBA and BALB mice. The duration of loss of righting reflex was, however, differentially affected in all three strains by naltrexone.

The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism.

Ethanol is proposed to exert its pharmacological effects by increasing membrane fluidity. Support for this hypothesis comes from strong correlations between in vitro effects of ethanol and pharmacological effects and genetic variation seen in vivo. Because arachidonate acid (AA) cascade is a membrane-bound system activated by disruptions in the cell membrane, it is possible that ethanol-induced membrane fluidization increases the formation of AA metabolites such as prostaglandins.

RATIONALE: A recent in-vitro study demonstrated that the potent disulfide reducing agent, DL-dithiothreitol (DTT), may alter the structural stability of the GABA(B) receptor, probably inactivating the disulfide bonds between four cysteine residues located in the GABA(B1(a)) receptor structure. OBJECTIVES: The present study was designed to evaluate whether DTT treatment was capable of antagonizing some behavioral effects of pharmacological stimulation of the GABA(B) receptor.

BACKGROUND: Acute functional tolerance (AFT) to ethanol-induced hypnosis is one of the main factors that affect the duration of ethanol-induced loss of righting reflex (LRR: "sleep time"). Investigators who use duration of LRR as a measure of ethanol-induced sedation should consider the potential magnitude and time course of this neuroadaptation when interpreting their results. However, AFT to the hypnotic effects of ethanol has not been well characterized. The present study explored this form of AFT using a novel method of monitoring LRR in mice.

Different effects of moderate to high doses of gamma-hydroxybutyric acid, including sedation/hypnosis, have been found to be blocked by gamma-aminobutyric acidB (GABAB) receptor antagonists. The present study investigated whether the protective effect of GABAB receptor antagonists extends also to gamma-hydroxybutyric acid-induced mortality. To this aim, the present study investigated the effect of the GABAB receptor antagonist, (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 100 mg/kg, ip), on mortality induced by gamma-hydroxybutyric acid (1-6 g/kg, ip) in DBA mice.