Differential effects of bupropion on acquisition and performance of an active avoidance task in male mice.

Bupropion is an antidepressant drug that is known to aid smoking cessation, although little experimental evidence exists about its actions on active avoidance learning tasks. Our aim was to evaluate the effects of this drug on two-way active avoidance conditioning. In this study, NMRI mice received bupropion (10, 20 and 40mg/kg) or saline before a daily training session (learning phase, days 1-4) in the active avoidance task. Performance was evaluated on the fifth day (retention phase): in each bupropion-treated group half of the mice continued with the same dose of bupropion, and the other half received saline. Among the vehicle-treated mice, different sub-groups were challenged with different doses of bupropion. Results indicated that mice treated with 10 and 20mg/kg bupropion exhibited more number of avoidances during acquisition. The response latency confirmed this learning improvement, since this parameter decreased after bupropion administration. No differences between groups were observed in the retention phase. In conclusion, our data show that bupropion influences the learning process during active avoidance conditioning, suggesting that this drug can improve the control of emotional responses.

Differential sensitivity to the effects of nicotine and bupropion in adolescent and adult male OF1 mice during social interaction tests.

Few studies have compared the action of both nicotine (NIC) and bupropion (BUP), an antidepressant used to treat NIC dependence, on social and aggressive behavior at different ages. This study aims to determine whether these drugs produce differential effects in adolescent (postnatal day: 36-37) and adult (postnatal day: 65-66) mice that have been housed individually for 2 weeks in order to induce aggressive behavior. Mice received BUP (40, 20, or 10 mg/kg), NIC (1, 0.5, and 0.25 mg/kg as base), or vehicle earlier to a social interaction test. BUP (40 mg/kg) decreased social investigation and increased nonsocial exploration in both adolescent and adult mice. The same effects were also observed in adult mice administered with a lower dose of the same drug (20 mg/kg). In adolescents, NIC (1 mg/kg) decreased social investigation, but this effect did not reach statistical significance in adults. In conclusion, a differential sensitivity to the effects of NIC or BUP emerged in some of the behavioral categories when the two age groups were compared.

Effects of acute bupropion administration on locomotor activity in adolescent and adult mice.

Responses to some psychoactive substances seem to differ between adolescents and adults. Bupropion, an antidepressant which is also used for smoking cessation, induces a dose-dependent increase in locomotor activity in adult mice, although its behavioral actions in adolescents have not been evaluated. In the present study the effects of acute bupropion administration (5, 10, 15 and 20 mg/kg) on locomotor activity were examined in early adolescent (postnatal day (pnd): 29-31 days), late adolescent (pnd: 47-49 days) and adult (pnd > 70 days) male NMRI mice, using an infrared photocell system. Locomotion was recorded for a total period of 90 min. Results indicated that there were significant differences in motor activity counts between the three ages evaluated, with late adolescents being more active than early adolescents. Bupropion (at doses 20, 15 and 10 mg/kg) induced a significant increase in locomotion, but there was no significant interaction between age and treatment. This suggests that the locomotor-stimulating effects of bupropion can be observed at different ages (early adolescence, late adolescence and adulthood), although the detailed analysis of the temporal course of locomotion changes induced by different bupropion doses reflected some differences between ages. The lowest dose (5 mg/kg) failed to induce hyperactivity in either adolescent or adult mice.

Spatial learning in male mice with different levels of aggressiveness: effects of housing conditions and nicotine administration.

The main aim of the present investigation was to evaluate the possible modulation of spatial learning ability by housing conditions and level of aggressiveness in mice, also testing whether differences in locomotion and anxiety could influence this relationship. Additionally, we have examined effects of nicotine in the acquisition and retention of a spatial learning task in groups of mice differing in these variables. NMRI male mice were either group-housed or individually housed for 30 days and then classified into mice with short (SAL) and long (LAL) attack latency after a pre-screening agonistic encounter. Locomotor activity and baseline levels of anxiety of these groups were evaluated in the actimeter and elevated plus-maze. Results indicated that SAL and LAL individually housed mice displayed higher locomotion activity than LAL group-housed mice. In the plus-maze test, SAL and LAL individually housed mice showed more total and open arm entries than group-housed LAL mice, confirming the hyperactivity of individually housed mice and suggesting that isolation had no clear anxiolytic or anxiogenic actions. In the water-maze, we compared the performance of individually housed SAL, individually housed LAL mice, and group-housed LAL mice treated with nicotine (0.35 and 0.175 mg/kg) or vehicle. Nicotine did not improve acquisition in group-housed mice and even impaired it in individually housed mice. Retention of platform position was better in vehicle-treated individually housed mice in comparison with vehicle-treated group-housed mice. The present study demonstrates that housing conditions but not level of aggressiveness modify spontaneous locomotor activity and behaviors displayed on the elevated plus-maze test, and can also influence retention of a spatial learning task.

Effects of early spatial training on water maze performance: a longitudinal study in mice.

The aim of the present study is to establish whether in mice the effects of an early experience in the Morris water maze are maintained after a long period. A longitudinal study was performed in which mice of two different strains (NMRI and C57) received spatial training at 2 months of age and their performance was re-evaluated 8 and 16 months later. In both strains, results showed a beneficial effect of prior experience on this spatial memory task even 8 months after the initial training. At 18 months of age, performance of C57 mice that were trained at 2 months of age for the first time was similar to those who received their first training at 10 months of age. These findings suggest that the beneficial effect of previous training could be limited by time. In addition, water maze performance of 18 month-old C57 mice did not differ from their earlier performance when they were 10 months of age, which would indicate that experience in this task could prevent some of the age-related spatial learning deficits observed in mice.

Time estimation and aging: a comparison between young and elderly adults.

Studies about effects of aging on the estimation of short temporal intervals are not conclusive. The aim of the present research was to evaluate age-related differences in the reproduction of a short interval (10 s) using a computerized method. The sample comprised thirteen young adults (M = 26.15 years) and twelve elderly adults (M= 79.1 years). Three parameters of time estimation were measured: estimated time, absolute error, and standard deviation. Results showed that time estimates performed by elderly participants were shorter than those of younger ones, although there were no significant differences between the two age groups in the percentage of absolute errors or standard deviations. These findings could be explained by changes in the rate of the internal clock or to an interaction between more general changes in cognitive processes.

Estimation of short temporal intervals in Alzheimer's disease.

This study investigated the estimation of short temporal intervals in Alzheimer's disease (AD). Eight patients with dementia of the Alzheimer type, and eight age-matched controls were evaluated in a time-estimation task. The task consisted in the production of three short empty intervals (5, 10, and 25 s). Results indicated that AD patients show deficits both in the accuracy and precision of time judgments: in the three intervals evaluated, the magnitude of absolute error and the variability in time judgments were significantly greater in AD patients than healthy respondents (p < .01). These findings are discussed taking into account the contribution of attentional processes during the performance of temporal tasks. It is concluded that the estimation of short temporal intervals could be useful as an objective indicator of cognitive decline in AD.

Previous training in the water maze: differential effects in NMRI and C57BL mice.

It has been shown that acquisition rates in the water maze vary across strains of mice, although the differential effects of previous experience in this spatial task have been scarcely evaluated. The aim of the present study was to evaluate the effects of training in the water maze at an early age (2 months) in two strains of mice (NMRI and C57BL) using a longitudinal study. Mice with or without previous training were tested when they were 6 months, and retested when 10 months old. The results showed that trained NMRI mice performed better than all the other groups, both at test and retest, indicating that previous training had more beneficial effects in NMRI than in C57BL mice. These results demonstrate that the effects of an early training in the water maze may be influenced by the characteristics of the strain of mice. It could have implications in longitudinal studies evaluating effects of pharmacological or behavioral manipulations.

Effects of nicotine on spatial learning in C57BL mice.

In the present study, the effects of nicotine on spatial memory in C57BL/6J mice was evaluated. Mice were trained in a water maze during four daily sessions of three trials each. In the first experiment, nicotine (0.7 and 0.35 mg/kg) or saline was administered once daily for 4 days, 15 min before the start of daily training: an impairment of performance of the water maze was observed in the group treated with 0.7 mg/kg of nicotine. In the second experiment, nicotine (0.7 and 0.35 mg/kg) or saline was administered from the 5 days prior to the beginning of the task and during the 4 days of acquisition. The results indicated an improvement in the rate of learning in the 9-day nicotine treated groups. The comparison between 4-day and 9-day treated groups revealed that the group receiving 0.35 mg/kg of nicotine for 9 days displayed significantly shorter latencies than all the other groups, while the group receiving 0.7 mg/kg of nicotine for 4 days performed significantly worse than all the other groups. The most noteworthy result is that nicotine was more effective after a more prolonged administration than when administered only during the training days.

A computerized system for measuring time perception in human subjects.

We describe an integrated computerized approach to the design, execution and recording of time perception experiments in human subjects. The program is menu driven and runs on an IBM-compatible microcomputer. The method is easy to use, non-obtrusive to the subjects, and flexible enough to allow the investigator to design studies with a wide range of experimental protocols and study parameters. The fact that the results do not depend on proctor bias or subject-proctor interactions are additional advantages. The technique was applied to study the effects of prompt positive feedback on the time perception of normal human subjects who undergo training. The results of this study are reported.

Sulpiride has an antiaggressive effect in mice without markedly depressing motor activity.

The atypical neuroleptic, sulpiride is a selective D2 antagonist, having a preferential action on mesolimbic regions. The effects of acute and chronic treatment with sulpiride on aggressive behaviour in male mice were studied using an ethologically based analysis. It was hypothesized that sulpiride would diminish "threat" and "attack" but would not produce marked "immobility", because of the mesolimbic effect referred to above. Isolated albino male mice (experimental animals) were confronted by "standard opponents". Acutely-treated experimental animals received an intraperitoneal injection of sulpiride (20, 50 or 100 mg/kg) 30 min before testing. Chronically-treated animals received sulpiride (10, 20 or 50 mg/kg) once a day for 7 or 14 consecutive days. Acute treatment with sulpiride had an obvious antiaggressive effect, with significantly decreased time devoted to "attack" and "threat" behaviour. Although time spent in "immobility" was modestly increased, the time devoted to other motor behaviour was also increased. Chronic treatment for 1 or 2 weeks did not change any behavioural category, except "immobility". The antiaggressive action of acutely administered sulpiride is interpreted as a relatively specific dopaminergic antagonist effect and not as merely a non-specific correlate of its disruptive action on motor behaviour. The possible anxiolytic action of sulpiride is also discussed.