CB1 cannabinoid receptors modulate kinase and phosphatase activity during extinction of conditioned fear in mice.
1. Learn Mem. 2004 Sep-Oct;11(5):625-32.
CB1 cannabinoid receptors modulate kinase and phosphatase activity during
extinction of conditioned fear in mice.
Cannich A(1), Wotjak CT, Kamprath K, Hermann H, Lutz B, Marsicano G.
Author information:
(1)Groups of Molecular Genetics of Behavior, Max Planck Institute of Psychiatry,
80804 Munich, Germany.
Cannabinoid receptors type 1 (CB1) play a central role in both short-term and
long-term extinction of auditory-cued fear memory. The molecular mechanisms
underlying this function remain to be clarified. Several studies indicated
extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase
with its downstream effector AKT, and the phosphatase calcineurin as potential
molecular substrates of extinction behavior. To test the involvement of these
kinase and phosphatase activities in CB1-dependent extinction of conditioned fear
behavior, conditioned CB1-deficient mice (CB1(-/-)) and wild-type littermates
(CB1(+/+)) were sacrificed 30 min after recall of fear memory, and activation of
ERKs, AKT, and calcineurin was examined by Western blot analysis in different
brain regions. As compared with CB1(+/+), the nonreinforced tone presentation 24
h after auditory-cued fear conditioning led to lower levels of phosphorylated
ERKs and/or calcineurin in the basolateral amygdala complex, ventromedial
prefrontal cortex, dorsal hippocampus, and ventral hippocampus of CB1(-/-). In
contrast, higher levels of phosphorylated p44 ERK and calcineurin were observed
in the central nucleus of the amygdala of CB1(-/-). Phosphorylation of AKT was
more pronounced in the basolateral amygdala complex and the dorsal hippocampus of
CB1(-/-). We propose that the endogenous cannabinoid system modulates extinction
of aversive memories, at least in part via regulation of the activity of kinases
and phosphatases in a brain structure-dependent manner.
DOI: 10.1101/lm.77904
PMCID: PMC523082
PMID: 15466318 [Indexed for MEDLINE]