Importance of bioavailable calcium drinking water for the maintenance of bone mass in post-menopausal women.

The aim of this research was to establish the importance of calcium intake through mineral water on vertebral bone density in women. To this purpose, we examined 255 women divided into two groups: those regularly drinking a high calcium content mineral water (group A; no.=175) and those using different type of water with a lower calcium content (group B; no.=80). Their dietary daily calcium intake was determined by means of a validated questionnaire (N.I.H. Consensus statement) and vertebral bone density was measured by Dual-Energy X-ray absorptiometry (Unigamma-plus ACN densitometer). Women in group A ingested a significantly higher quantity of calcium in water than women in group B (mean difference 258 mg; 95% confidence limits: 147-370 mg). The average bone density values were slightly but significantly higher in group A as compared to group B (mean+/-SD: 1.044+0,15 vs 1.002+0,14; p=0.03). In addition to age, BMI and menopausal status, calcium intake was a significant predictor of spinal BMD. These 4 variables explained about 35% of the spinal BMD variance. When the analysis was repeated separately for pre- and post-menopausal subjects, calcium remained a significant predictor in post-menopausal women (t=2.28; p=0.02), but not in premenopausal women. These results underline the importance of a lifelong daily calcium intake, resulting by the regular drinking of high bioavailable calcium water, in order to maintain bone mass after the menopause, in comparison to the use of a lower content calcium water.

Chronic morphine affects working memory during treatment and withdrawal in rats: possible residual long-term impairment.

An eight-arm radial maze was used to investigate a possible short-term (during the development of tolerance and dependence) and long-term (6, 9 and 12 months after treatment) effect on working memory, in young rats, which drank morphine (0.5mg/ml) for 1 month, or to which the drug was administered by i.p. injection (at weekly increasing doses of 20, 50, 100, 200mg/kg). Tail flick test and cortically derived electroencephalographic (EEG) recordings were also carried out in the same rats to determine any modifications in analgesia and in total EEG mean power spectra during treatment and withdrawal. Complete tolerance to morphine analgesia developed during the period of drug treatment. Chronic morphine significantly impaired radial maze performance in the working memory components of the task during both treatment and early withdrawal, but only in the i.p. group. Six and 9 months after morphine treatment, both the oral and i.p. group showed a significant impairment of radial maze performance. The mean power spectra were altered during treatment but returned to baseline values during abstinence, except for the first day. These findings suggest the possibility of morphine-induced premature ageing, which is more evident in i.p. treated animals. The mechanism by which morphine treatment produces residual long-term learning impairment requires further elucidation.

Possibility of spontaneous drug abuse tested in rat.

Given that a number of the techniques used to test drug abuse liability are not free from criticism, a series of oral free-choice experimental procedures was adopted. When simultaneously offered as alternatives to glucose using the classical polydipsic procedure, no preference for buprenorphine (0.025 mg/ml), morphine (0.5 mg/ml) or fentanyl (0.005 mg/ml) solutions was shown by premedicated rats. The same result was obtained when the two-bottle procedure was used for at least one month to offer etonitazene (10 micrograms/ml), buprenorphine (60 micrograms/ml), cocaine (300 micrograms/ml) and haloperidol (25 micrograms/ml) solutions as simultaneous alternatives to aspartame. This absence of preference was maintained even when the rats showed evident pharmacological effects and, in the case of the opiates, tolerance and withdrawal syndrome. However, when a gustatory marker (quinine) was introduced into one of the two solutions, preference was always shown for the other. Finally, in a conditioned taste aversion (CTA) test, etonitazene (5 or 40 micrograms/kg, i.p.) and haloperidol (0.5 or 2 mg/kg, i.p.) did not induce any reduction in saccharin consumption, while morphine (40 mg/kg) did. Pretreatment with naloxone (120 micrograms/kg, i.c.v.) did not antagonize morphine-induced CTA, while it did antagonize morphine-induced analgesia.

Dose-dependent conditioned place preference produced by etonitazene and morphine.

The conditioned place preference (CPP) paradigm was used to study the reinforcing properties of etonitazene in comparison with those of morphine. Increasing doses of etonitazene (2.5-15 micrograms/kg i.p.) and morphine (1-80 mg/kg i.p.) induced a dose-dependent CPP. High doses of etonitazene (25-40 micrograms/kg) did not elicit CPP. In addition, these reinforcing properties were related to behavioral modifications such as analgesia, assessed with the tail-flick method, and increased catalepsy, evaluated by a scoring system. It is concluded that neither the strong behavioral effects induced by etonitazene nor tolerance to such effects account for the results. These findings are discussed with regard to the possibility that etonitazene could interfere with associative learning motivated by reward.

Effect of centrally administered atropine and pirenzepine on radial arm maze performance in the rat.

The effect of two anticholinergic drugs administered intracerebroventricularly on acquisition of an 8-arm radial maze task was examined in the rat. Increasing doses of atropine (1, 4.5, 22.5, 45 micrograms/rat) and pirenzepine (4.5, 15, 60, 90 micrograms/rat) significantly impaired performance in the working-memory components of the task. For both drugs this impairment was linearly related to the log of the administered doses and log-dose-response relationship were parallel. The regression lines calculated for each parameter for both drugs were parallel to each other, thus allowing us to calculate the potency of atropine versus pirenzepine: atropine was 5.4 times more potent than pirenzepine for correct arm entries, 10 times more potent for the number of errors and 4 times more potent for the total time taken to complete the task. The relevance of M1 and M2 subtype central acetylcholine receptors in cognitive processes is discussed.

Central effect of yohimbine on sexual behavior in the rat.

A large range of doses of yohimbine (Y) was administered intracerebroventricularly (ICV) (5-100 micrograms/rat) or intraperitoneally (IP) (0.35-10 mg/kg) to male rats and the effects on sexual, locomotor and general behavior were evaluated. For both routes there was a clear-cut inverted-U effect (stimulating/depressing), calculable as parabolic regressions on the log of administered doses. The maximal stimulating doses (15 micrograms/rat ICV and 1 mg/kg IP) significantly shortened mount, intromission and ejaculation latencies and the mean interintromission interval. These data indicate the importance of CNS mechanisms in the sexual effect of Y.