Involvement
of neuronal plasticity in stress and the action
of antidepressants
The
action of most antidepressants resides in
changes of the levels of monoamine
neurotransmitters in the brain. However, there
is increasing evidence that they also modulate
the neurotransmission of glutamate which is the
most abundant neurotransmitter in the brain.
Recent research has investigated the effect of
stress or antidepressants on the synaptic
transmission in the hippocampus, part of the
limbic system involved in cognitive functions,
attention and affect. In particular the study
focussed on the two main mediators of synaptic
plasticity, the N-methyl-D-aspartate (NMDA)
receptor complex for glutamate and the
Ca2+/calmodulin-dependent protein
kinase II (CaM kinase II).
Both stress and antidepressants caused
alterations in long-term potentiation of
glutamatergic synapses which could be the
consequence of the stimulation of monoaminergic
pathways projecting to the hippocampus.
Particularly following antidepressant
treatments, synaptic changes in the NMDA
receptor and CaM kinase II have been observed,
mainly exerted by brain-derived neurotrophic
factor (BDNF). BDNF plays a key role in
modulating the synaptic plasticity and its
molecular mediators and also in inducing the
morphological synaptic modifications.
These findings could lead to the investigation
of new molecular targets for drugs acting to
treat the mood
disorders. Bipolar
Disord 4: 166, 2002