Mice lacking the adenosine A₁ receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate

Abstract

Behavioural assessment of mice lacking adenosine A1 receptors (A1Rs) showed reduced activity in some phases of the light-dark cycle, reduced exploratory behaviour in the open-field and in the hole-board, increased anxiety in the plus maze and dark-light box and increased aggressiveness in the resident-intruder test. No differences were found in spatial reference and working memory in several Morris water maze tasks. Both mutant mice had reduced muscle strength and survival rate. These results confirm the involvement of adenosine in motor activity, exploratory behaviour, anxiety and aggressiveness. A1Rs also appear to play a critical role in ageing-related deterioration.

Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly

“…During the 6 min of the first test, they visited most of the six arms, made some reentries, and explored several short, blind alleys. These results may be in contrast to the higher and lower activities observed in A 1 R +/− and A 1 R −/− , respectively, in the open-field and the hole-board tests (see Giménez-Llort et al, 2002). Nevertheless, the exploratory behavior measured in those tests is mixed with a certain level of anxiety/emotionality which depends, for instance, on how different the apparatus is from the natural environment, the level of illumination, and the open space.…”

“…Nevertheless, the exploratory behavior measured in those tests is mixed with a certain level of anxiety/emotionality which depends, for instance, on how different the apparatus is from the natural environment, the level of illumination, and the open space. In fact, no differences in exploratory activity were found during the first hours in activity meter cages (see Giménez-Llort et al, 2002), which were very similar to their own home-cages. In the same way, the dark tunnel maze resembling the natural mouse burrows would allow us to measure the exploratory behavior without (or with less) interference of anxiety/emotionality.…”

“…Therefore, it is interesting that several recent articles have reported little or no effect of deletion of the A 1 R on learning and memory (Giménez-Llort et al, 2002;Lang et al, 2003), despite the fact that at least some forms of LTP are strongly affected (Moore et al, 2003). In the present study the role of A 1 Rs in these processes has therefore been reexamined.…”

“…They were maintained at an ambient room temperature of 22 ± 2°C with 60 ± 10% relative humidity and an inverse 12-h light/dark (LD) schedule with lights on at 15:00 h. The animals had lab chow and tap water ad libitum until the moment of the test. Behavioral screening started at 5 months of age (see Giménez-Llort et al, 2002) and when the animals were 9 months old they were successively confronted with several learning and memory tests: place learning for reference memory, removal, reversal, cue learning, and place learning for working memory in the Morris water maze, over weeks 35-38, and a sixarm radial tunnel maze during week 74. The experiments were performed under dim white light during their light phase of the LD cycle (17:00-21:00 h).…”

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

“…Future aging studies (rather than comparisons between groups of adult and aged animals) will be required to elucidate these issues. This might be particularly relevant in view of the observation that A 1 Rs seem to control the life-span of mice, since the life expectancy of A 1 R knockout mice is significantly lower than that of their wild-type littermates [388].…”