Striatopallidal cannabinoid type-1 receptors mediate amphetamine-induced sensitization
Current Biology. 2023-11-01; 33(22): 5011-5022.e6
DOI: 10.1016/j.cub.2023.09.075
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Mariani Y(1), Covelo A(1), Rodrigues RS(1), Julio-Kalajzić F(1), Pagano Zottola AC(2), Lavanco G(3), Fabrizio M(4), Gisquet D(1), Drago F(5), Cannich A(1), Baufreton J(6), Marsicano G(7), Bellocchio L(8).
Author information:
(1)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France.
(2)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France;
Institut de Biochimie et Génétique Cellulaires, UMR 5095, 33077 Bordeaux, France.
(3)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France;
University of Palermo, Department of Health Promotion, Mother and Child Care,
Internal Medicine and Medical Specialties of Excellence « G. D’Alessandro, » 90127
Palermo, Italy.
(4)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France;
Center for Interdisciplinary Research in Biology (CIRB), College de France,
CNRS, INSERM, 5 Université PSL, 75231 Paris, France.
(5)Department of Biomedical and Biotechnological Sciences, Section of
Pharmacology, University of Catania, Catania 95124, Italy.
(6)Univ. Bordeaux, CNRS, IMN, UMR 5293, 33000 Bordeaux, France.
(7)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France.
Electronic address: .
(8)Univ. Bordeaux, INSERM, Neurocentre Magendie, U1215, 33000 Bordeaux, France.
Electronic address: .
Repeated exposure to psychostimulants, such as amphetamine, causes a
long-lasting enhancement in the behavioral responses to the drug, called
behavioral sensitization.1 This phenomenon involves several neuronal systems and
brain areas, among which the dorsal striatum plays a key role.2 The
endocannabinoid system (ECS) has been proposed to participate in this effect,
but the neuronal basis of this interaction has not been investigated.3 In the
CNS, the ECS exerts its functions mainly acting through the cannabinoid type-1
(CB1) receptor, which is highly expressed at terminals of striatal medium spiny
neurons (MSNs) belonging to both the direct and indirect pathways.4 In this
study, we show that, although striatal CB1 receptors are not involved in the
acute response to amphetamine, the behavioral sensitization and related synaptic
changes require the activation of CB1 receptors specifically located at
striatopallidal MSNs (indirect pathway). These results highlight a new mechanism
of psychostimulant sensitization, a phenomenon that plays a key role in the
health-threatening effects of these drugs.
Copyright © 2023 Elsevier Inc. All rights reserved.
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.