Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.
Proc Natl Acad Sci USA. 2016-08-15; 113(35): 9904-9909
DOI: 10.1073/pnas.1525066113
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1. Proc Natl Acad Sci U S A. 2016 Aug 30;113(35):9904-9. doi:
10.1073/pnas.1525066113. Epub 2016 Aug 15.
Peripheral and central CB1 cannabinoid receptors control stress-induced
impairment of memory consolidation.
Busquets-Garcia A(1), Gomis-González M(2), Srivastava RK(3), Cutando L(2),
Ortega-Alvaro A(2), Ruehle S(3), Remmers F(3), Bindila L(3), Bellocchio L(4),
Marsicano G(4), Lutz B(3), Maldonado R(2), Ozaita A(5).
Author information:
(1)Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and
Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
Endocannabinoids and Neuroadaptation Group, NeuroCentre Magendie, INSERM U1215,
33077, Bordeaux, France;
(2)Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and
Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
(3)Institute of Physiological Chemistry, University Medical Center of the
Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
(4)Endocannabinoids and Neuroadaptation Group, NeuroCentre Magendie, INSERM
U1215, 33077, Bordeaux, France;
(5)Laboratory of Neuropharmacology-NeuroPhar, Department of Experimental and
Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain;
.
Stressful events can generate emotional memories linked to the traumatic
incident, but they also can impair the formation of nonemotional memories.
Although the impact of stress on emotional memories is well studied, much less is
known about the influence of the emotional state on the formation of nonemotional
memories. We used the novel object-recognition task as a model of nonemotional
memory in mice to investigate the underlying mechanism of the deleterious effect
of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade
of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory
impairment. Genetic deletion and rescue of CB1 receptors in specific cell types
revealed that the CB1 receptor population specifically in dopamine β-hydroxylase
(DBH)-expressing cells is both necessary and sufficient for stress-induced
impairment of memory consolidation, but CB1 receptors present in other neuronal
populations are not involved. Strikingly, pharmacological manipulations in mice
expressing CB1 receptors exclusively in DBH(+) cells revealed that both
hippocampal and peripheral receptors mediate the impact of stress on memory
consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide
previously unrecognized cross-talk between central and peripheral mechanisms in
the stress-dependent regulation of nonemotional memory consolidation, suggesting
new potential avenues for the treatment of cognitive aspects on stress-related
disorders.
DOI: 10.1073/pnas.1525066113
PMCID: PMC5024630
PMID: 27528659 [Indexed for MEDLINE]
Conflict of interest statement: The authors declare no conflict of interest.