Presynaptic homeostatic plasticity rescues long-term depression after chronic Delta 9-tetrahydrocannabinol exposure.
Alterations of long-term synaptic plasticity have been proposed to participate in the development of addiction. To preserve synaptic functions, homeostatic processes must be engaged after exposure to abused drugs. At the mouse cortico-accumbens synapses, a single in vivo injection of Delta9-tetrahydrocannabinol (THC) suppresses endocannabinoid-mediated long-term depression. Using biochemical and electrophysiological approaches, we now report that 1 week of repeated in vivo THC treatment reduces the coupling efficiency of cannabinoid CB1 receptors (CB1Rs) to G(i/o) transduction proteins, as well as CB1R-mediated inhibition of excitatory synaptic transmission at the excitatory synapses between the prefrontal cortex and the nucleus accumbens (NAc). Nonetheless, we found that cortico-accumbens synapses unexpectedly express normal long-term depression because of a reversible switch in its underlying mechanisms. The present data show that, in THC-treated mice, long-term depression is expressed because a presynaptic mGluR2/3 (metabotropic glutamate receptor 2/3)-dependent mechanism replaces the impaired endocannabinoid system. Thus, in the NAc, a novel form of presynaptic homeostasis rescues synaptic plasticity from THC-induced deficits.
Mato
Susana
S
Institut National de la Santé et de la Recherche Médicale Equipe Avenir (Plasticité Synaptique: Maturation and Addiction), Institut Magendie des Neurosciences, 33077 Bordeaux Cedex, France.
Robbe
David
D
Puente
Nagore
N
Grandes
Pedro
P
Manzoni
Olivier J
OJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage*; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology
D013759:Dronabinol