Effects of amphetamine on the plus-maze discriminative avoidance task in mice.

RATIONALE: The contradictory amphetamine effects on memory could be due to different protocols of amphetamine administration or the well-known anxiogenic effect of the drug. OBJECTIVE: The effects of different protocols of administration of amphetamine were investigated on mice tested in the plus-maze discriminative avoidance task (DAT), which provides simultaneous information about memory and anxiety. METHODS: Acutely pre- or post-training, 0.3, 1.0, or 3.0 mg/kg amphetamine-treated, 10-day chronically 3.0 mg/kg amphetamine-treated, 0.3 mg/kg amphetamine plus 0.25 mg/kg scopolamine and 3.0 mg/kg amphetamine plus 3.0 mg/kg tacrine-treated mice were conditioned to choose between two enclosed arms (one of which was aversive) while avoiding two open arms. Learning/memory was evaluated by the percentage time in the aversive enclosed arm (PTAV), and anxiety by the percentage time in the open arms (PTO). RESULTS: Given acutely before conditioning, amphetamine significantly decreased PTO in training, suggesting an anxiogenic effect, and significantly increased PTAV in the test, suggesting an amnestic action. Given acutely after the conditioning, no action of this drug on memory was found. After repeated treatment, the anxiogenic effect disappeared, while the amnestic effect remained. While no effects of subeffective doses of amphetamine and scopolamine co-administration were detected, tacrine attenuated the amnestic effect of amphetamine. CONCLUSIONS: Amphetamine has different effects on DAT when given pre- or post-training. While acute pre-training amnestic action is temporally correlated with an anxiogenic effect, there is tolerance to the anxiogenic but not to the amnestic effect after repeated administration. Because this acute amnestic effect of amphetamine is attenuated by tacrine, a possible relationship with cholinergic system cannot be discarded as a mechanism to amphetamine-induced amnesia in DAT.

Long-term accumulation and microdistribution of uranium in the bone and marrow of beagle dog.

The accumulation and microdistribution of uranium in the bone and marrow of Beagle dogs were determined by both neutron activation and neutron-fission analysis. The experiment started immediately after the weaning period, lasting till maturity. Two animal groups were fed daily with uranyl nitrate at concentrations of 20 and 100 microg g(-1) food. Of the two measuring techniques, uranium accumulated along the marrow as much as in the bone, contrary to the results obtained with single, acute doses. The role played by this finding for the evaluation of radiobiological long-term risks is discussed. It was demonstrated, by means of a biokinetical approach, that the long-term accumulation of uranium in bone and marrow could be described by a piling up of single dose daily incorporation.

The diphenhydramine-induced decrease in general open-field activity of female rats is gonadal steroid dependent.

The effect of ovarian steroids on sedative effects of diphenhydramine (D), a histamine H1 receptor blocker, was determined. Seventy-five female Wistar rats were randomly divided into three groups: Group 1 (N = 54) was ovariectomized, group 2 (N = 7) was sham-operated, and group 3 (N = 14) was intact. The ovariectomized rats were then subdivided into 4 groups. Two groups received peanut oil 54 and 6 h before treatment with saline solution (group OS) or 20 mg/kg D (group OD). The other two groups received 50 micrograms/kg 17-beta-estradiol and 2 mg/kg progesterone, respectively, 54 and 6h before treatment with saline solution (group OHS) or 20 mg/kg D (group OHD). The sham-operated animals were treated as the OS group. Intact animals were injected with saline (group IS) or 20 mg/kg D (group ID) on the day of estrus, as determined by vaginal smears taken in the morning before the behavioral observations. Rats were observed for 6 min in the open field during the dark period of the cycle, 15 min after the administration of saline or D. There was a similar decrease in locomotion and rearing frequencies in OHS vs OHD and IS vs ID groups. Nevertheless, a lack of D sedative effect was observed in OD rats (locomotion and rearing frequencies, 56.0 +/- 3.3 vs 46.1 +/- 3.8 and 15.5 +/- 1.6 vs 15.2 +/- 1.6., for OS and OD groups, respectively). The results suggest that the sedative effect of diphenhydramine depends on the presence of ovarian steroids.

The diphenhydramine-induced decrease in general open-field activity of female rats is gonadal steroid dependent

The effect of ovarian steroids on sedative effects of diphenhydramine (D), a histamine H1 receptor blocker, was determined. Seventy-five female Wistar rats were randomly divided into three groups: Group 1 (N = 54) was ovariectomized, group 2 (N = 7) was sham-operated, and group 3 (N = 14) was intact. The ovariectomized rats were then subdivided into 4 groups. Two groups received peanut oil 54 and 6 h before treatment with saline solution (group OS) or 20 mg/kg D (group OD). The other two groups received 50 micrograms/kg 17-beta-estradiol and 2 mg/kg progesterone, respectively, 54 and 6h before treatment with saline solution (group OHS) or 20 mg/kg D (group OHD). The sham-operated animals were treated as the OS group. Intact animals were injected with saline (group IS) or 20 mg/kg D (group ID) on the day of estrus, as determined by vaginal smears taken in the morning before the behavioral observations. Rats were observed for 6 min in the open field during the dark period of the cycle, 15 min after the administration of saline or D. There was a similar decrease in locomotion and rearing frequencies in OHS vs OHD and IS vs ID groups. Nevertheless, a lack of D sedative effect was observed in OD rats (locomotion and rearing frequencies, 56.0 +/- 3.3 vs 46.1 +/- 3.8 and 15.5 +/- 1.6 vs 15.2 +/- 1.6., for OS and OD groups, respectively). The results suggest that the sedative effect of diphenhydramine depends on the presence of ovarian steroids