Acetylcholine neurotransmission is considered to play a critical role
in processes underlying behavioural activity, arousal, attention, lear
ning, and memory. These functional attributions have largely been base
d on pharmacological findings, or data from brain damaged animals, and
humans with neurodegenerative diseases, such as Alzheimer's disease.
With the introduction of the in vivo microdialysis method it has recen
tly become possible to monitor acetylcholine in the brain of the behav
ing animal, which allows to investigate its activity in specific behav
ioural tasks. With respect to learning and memory, one of the most ele
mentary experimental paradigms is that of behavioural habituation, whe
re the decrease of exploratory activity as a function of repeated expo
sure to the same environment is taken as an index of memory. We have u
sed this paradigm to monitor hippocampal acetylcholine levels by means
of in vivo microdialysis in rats, which were exposed to a novel open
field and which were re-exposed to it on the following day (10 min eac
h). The results show that exposure of rats to the novel environment le
d to increased extracellular levels of hippocampal acetylcholine which
were positively correlated with exploratory behaviour. These choliner
gic activations were larger than those of control animals which were h
andled like the experimental animals but which were not exposed to the
open held. When re-exposing the experimental animals to the same envi
ronment, exploratory behaviour, but not cholinergic activation, was de
creased, indicating habituation. In the subsequent 10 min, that is, wh
en the animals where back in their home cages, cholinergic activity wa
s still increased. The magnitude of increase was larger after re-expos
ure than after exposure to the novel open field. Finally, we different
iated the animals into ''superior'' vs ''inferior'' learners and found
that the ''superior'' learners showed higher behavioural activation i
n the novel environment and stronger neurochemical responses, both, in
the novel and familiar environment. Our data show that extracellular
levels of hippocampal acetylcholine are not only elevated in relation
to novelty and behavioural activation, but also during behavioural hab
ituation. Furthermore, an interindividual variability of cholinergic a
ctivation seems to exist which is related to individual differences in
behavioural responsiveness to novelty. Such differences in cholinergi
c activity may be related to other known differences in hippocampal st
ructure and function and may be important for previously reported inte
r-individual variabilities in sensation-seeking and related mnestic fu
nctions. (C) 1998 IBRO. Published by Elsevier Science Ltd.