Search

Ts65Dn (TS), control littermates (CO) and Swiss (SW) male mice were tested in the elevated plus-maze and in the Morris water maze (MWM) for memory evaluation. In the plus-maze, each mouse was placed at the end of an open arm and initial freezing and the time to enter into an enclosed arm (transfer latency) were measured. SW mice decreased both measures over repeated trials, whereas no decrease of freezing was observed in CO mice, thus suggesting increased emotionality in this group. Compared to CO mice, TS mice showed less initial freezing, shorter transfer latencies, and spent less time in enclosed arms, suggesting a reduced ability to habituate or to inhibit behaviour. Animals were also submitted to a learning-set paradigm consisting of reaching a new platform position each day in the MWM. Two training phases (separated by a resting period of 6 weeks), each including eight acquisition and four cued sessions, were performed (each session consisting of four pairs of trials). CO and SW mice already reached an asymptotic performance by the second day of the first phase whereas TS mice did not achieve that level until the second training phase. The progression over trials indicated that CO and SW animals learned the new platform position between trials 1 and 2 of each session, whereas TS animals failed to do it and had more difficulties to find the platform when it was placed in the centre of the pool as compared to the other positions (SW, NE, E). The results suggest that TS mice show working memory impairments in addition to long-term memory deficits, although extensive training appeared to facilitate TS mice to achieve a level of performance similar to their control littermates. This represents another aspect of the cognitive deficits shown by TS mice: a mouse model of the human Down syndrome.

Mice which are trisomic for only the human chromosome (Chr) 21-homologous segment of mouse Chr 16 (segmental trisomy), including a portion of the Down syndrome region of human Chr 21, have recently been developed. Since these segmentally trisomic mice, designated Ts(17(16))65Dn, survive to adulthood, they may represent a mouse model for the study of Down syndrome. A partial characterization of their behavioral phenotype was undertaken by evaluating the sensorimotor reflexes, exploration, locomotor activity, emotionality and spatial learning in 16 male Ts65Dn mice (TS) and 16 control (CO) littermates. No sensorimotor deficits appeared in TS compared to CO mice. By contrast, head-dipping behaviour in the hold board was increased in TS mice with respect to the CO group, showing a higher repetition rate of previously explored holes. Crossings in the open field and total arm entries in the plus maze were higher in TS than in the CO group during the dark phase of the light-dark (LD) cycle under red light, but not during the light phase of the LD cycle under white light. Entries into the open arms of the plus maze were increased overall in TS mice when compared to CO mice, but no differences were found in time spent in the open arms. TS mice showed impaired place learning in the Morris water maze, whereas they were able to reach the same performance as CO animals in cued learning. Thus, absence of sensorimotor deficits, increased exploration, hyperactivity under certain experimental conditions and a moderate impairment of spatial learning were the principal characteristics observed in TS mice compared to their CO littermates.

The present study shows that postnatal handling (H: consisting of removing the pups from the nest twice daily and placing them individually in plastic cages lined with paper towel for a period of 10 min, between postnatal days 1 and 21) and/or environmental enrichment (E: for a period of 6 months) of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats induced long-lasting decreases in emotional reactivity (i.e. reduced defecations in the open field, OF, and hole-board, HB, tests) as well as increases in exploratory behavior (i.e. head-dipping) in a manner dependent upon the rat line (there were 'line x H' and 'line x E' interactions). It is reported for the first time that RHA/Verh rats show more head-dipping behavior than RLA/Verh rats, and that the environmental treatments can increase head-dipping of RLA/Verh animals to the level shown by RHA/Verh rats.

The present study shows that postnatal 'consistent' handling (CH; which consisted of removing the pups from the nest and placing them individually in plastic cages lined with paper towel for a period of 15 min daily between 1 and 22 postnatal days) of rats had long-lasting improving effects on coping with a stressful task (i.e. enhancement on the early acquisition of two-way active avoidance), but such effects were completely prevented when CH treatment was combined with chronic perinatal Ro 15-1788 (7 mg/kg/day, between prenatal day 19 and postnatal day 22) administration (i.e. blockade of benzodiazepine receptor (BZR)). A long-lasting decremental effect was also observed in the same task in rats which received postnatal 'inconsistent' handling (INCH; in which stimulation of pups was changed every day between 1 and 22 postnatal days), without being affected by the concomitant perinatal Ro 15-1788 treatment. These results suggest that intact ontogeny of BZRs is necessary to obtain the enduring positive effects of CH on emotional behavior (i.e. early acquisition of two-way active avoidance).