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Publication : Striatopallidal cannabinoid type-1 receptors mediate amphetamine-induced sensitization.

First Author  Mariani Y Year  2023
Journal  Curr Biol Volume  33
Issue  22 Pages  5011-5022.e6
PubMed ID  37879332 Mgi Jnum  J:349861
Mgi Id  MGI:7567131 Doi  10.1016/j.cub.2023.09.075
Citation  Mariani Y, et al. (2023) Striatopallidal cannabinoid type-1 receptors mediate amphetamine-induced sensitization. Curr Biol 33(22):5011-5022.e6
abstractText  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 (CB(1)) 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 CB(1) receptors are not involved in the acute response to amphetamine, the behavioral sensitization and related synaptic changes require the activation of CB(1) 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.
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