ELAV-GAP43 PATHWAY ACTIVATION FOLLOWING COMBINED EXPOSURE TO COCAINE AND STRESS.

Rationale An increasing body of evidence suggests that
drug addiction engages circuits also associated with
memory processes. In particular, in the hippocampus, a
substantial similarity seems to exist between the changes
yielded by drugs of abuse and those induced by hippocampaldependent
learning.
Objectives Considering the key involvement of neuronal
Embryonic Lethal Abnormal Vision (nELAV) proteins in
memory processes occurring within the hippocampus and
the critical role of stress for compulsive drug use and
relapse, we investigated the effect of cocaine and stress
challenges on the activation of the nELAV cascade.
Materials and methods Rats were treated subcutaneously
with vehicle or cocaine hydrochloride (20 mg/kg, once a
day for 2 weeks). Three days later, half of them were also
subjected to a single stress exposure. Western blotting and
real-time polymerase chain reaction (PCR) experiments
were performed on the hippocampi.
Results Our results show that the combination of repeated
exposure to cocaine and acute stress significantly enhances
nELAVexpression and phosphorylation in the hippocampus
with a concomitant increase of GAP43 expression (a
specific nELAV target), an effect that seems to involve,
upstream, protein kinase C alpha (PKCα). The activation of
this pathway occurs independently from widespread neuronal
activation since no alterations were observed in the
expression of the immediate early gene Arc (a widely
established index of neuronal activity), suggesting that the
activation of the nELAV–GAP43 cascade reflects a targeting
of specific processes rather than a global interference
with hippocampal homeostasis.
Conclusions Based on our results, we speculate that
cocaine and stress may recruit such a pathway, crucial for
physiological learning, potentially contributing to the
aberrant engagement of learning mechanisms observed in
drug addiction behavior.