Central histaminergic transmission modulates the expression of chronic nicotine withdrawal induced anxiety-like and somatic behavior in mice.

The present study investigated the plausible modulatory role of central histaminergic transmission on the expression of nicotine withdrawal induced anxiety and somatic behavior in mice. Abrupt cessation of chronic nicotine (2 mg/kg, i.p. × 3/day) treatment for 12 days to mice, expressed increased anxiety in light & dark test and total abstinence (somatic) score at 24 h post nicotine withdrawal time. The somatic signs includes a composite score of all behaviors such as grooming, rearing, jumping, body shakes, forelimb tremors, head shakes, abdominal constrictions, scratching, empty mouth chewing or teeth chattering, genital licking, tail licking. Mice exhibited higher expression to nicotine withdrawal induced anxiety in light & dark test at 24 h post-nicotine withdrawal time on pre-treatment centrally (i.c.v) with histaminergic agents like histamine (0.1, 50 µg/mouse), histamine H3 receptor inverse agonist, thioperamide (2, 10 µg/mouse), histamine H1 receptor agonist, FMPH (2, 6.5 µg/mouse) or H2 receptor agonist amthamine (0.1, 0.5 µg/mouse) or intraperitoneally (i.p.) with histamine precursor, l-histidine (250, 500 mg/kg) as compared to control nicotine withdrawn animals. Furthermore, mice pre-treated with all these histaminergic agents except histamine H1 receptor agonist, FMPH shows exacerbated expression to post-nicotine withdrawal induced total abstinence (somatic) score in mice. On the other hand, central injection of selective histamine H1 receptor antagonist, cetirizine (0.1 µg/mouse, i.c.v.) or H2 receptor antagonist, ranitidine (50 µg/mouse, i.c.v) to mice 10 min before 24 h post-nicotine withdrawal time completely alleviated the expression of nicotine withdrawal induced anxiety and somatic behavior. Thus, it can be contemplated that the blockade of central histamine H1 or H2 receptor during the nicotine withdrawal phase could be a novel approach to mitigate the nicotine withdrawal associated anxiety-like manifestations. Contribution of endogenous histamine via H1 or H2 receptor stimulation in the nicotine withdrawal induced anxiety and somatic behavior is proposed.

Magnesium taurate attenuates progression of hypertension and cardiotoxicity against cadmium chloride-induced hypertensive albino rats.

The present study was designed to evaluate the antihypertensive activity and cardioprotective effects of magnesium taurate against cadmium chloride (CdCl2)-intoxicated albino rats. Sprague Dawley male albino rats (120-150 g) were divided into five groups having six animals in each group. Hypertension and cardiotoxicity were induced in animals by administration of CdCl2 (0.5 mg/kg/day, i.p.) for four weeks. Magnesium taurate (2 and 4 mg/kg/day) was administered orally after induction of hypertension (after two weeks) in their respective groups concurrently with CdCl2 for next two weeks. Amlodipine (3 mg/kg/day, p.o.) was used as a standard and administered after induction of hypertension. Blood pressure was monitored biweekly by using non-invasive blood pressure system and biochemical parameters and histopathology of the heart were evaluated after four weeks of the experimental protocol. During the four weeks of the experimental protocol, the toxic control group showed significant elevation of systolic and diastolic blood pressure concomitant with augmentation of cardiotoxicity as indicated by reduction in myocardial antioxidants including glutathione peroxidase, catalase, superoxide dismutase, reduced glutathione and increased malondialdehyde level in heart as compared to the normal group. The oral administrations of magnesium taurate significantly restored the blood pressure, myocardial antioxidants and malondialdehyde level as compared to toxic control group. In addition, histopathological examination showed that magnesium taurate treatments substantially reduced the myocardial damages against CdCl2 treatment. The results suggest that magnesium taurate has prominent antihypertensive and cardioprotective activity via its potent antioxidant activity and can be used as a nutrition supplement to improve the cardiovascular health.