Cocaine-mediated synaptic potentiation is absent in VTA neurons from mGlu5-deficient mice.
Drugs of abuse have the ability to instantiate plastic adaptations within the central nervous system, and this property may relate to the development and persistence of addiction. In this context, a single exposure to cocaine in rodents may induce synaptic plasticity by increasing the AMPA/NMDA receptor excitatory post-synaptic current (EPSC) amplitude ratio in dopaminergic cells of the ventral tegmental area (VTA). Here, we examine the role of the metabotropic glutamate 5 (mGlu5) receptor in this regard using a genetic mouse model. The control AMPA/NMDA EPSC ratio is reduced in mGlu5-deficient mice compared to wild-types. Moreover, cocaine-induced enhancement of this EPSC ratio is also absent in mutant mice, which suggests that mGlu5 receptors are required for single-dose cocaine-induced plasticity onto VTA cells. While the temporal profile of hyperactivity to acute cocaine is altered in mGlu5-deficient mice; these mice still develop and express sensitized psychomotor responses to cocaine. These data suggest that the mGlu5 receptor is required for cocaine-induced plasticity in VTA dopaminergic cells. In contrast, the mGlu5 receptor may not be essential for psychostimulant behavioural sensitization; although it probably impacts other aspects drug addiction, such as motivation to self-administer.
Bird
Michael K
MK
Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.
Reid
Christopher A
CA
Chen
Feng
F
Tan
Heneu O
HO
Petrou
Steven
S
Lawrence
Andrew J
AJ
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D003042:Cocaine