title: Prefrontal synaptic markers of cocaine addiction-like behavior in rats.
abstract: Defining the drug-induced neuroadaptations specifically associated with the behavioral manifestation of addiction is a daunting task. To address this issue, we used a behavioral model that differentiates rats controlling their drug use (Non-Addict-like) from rats undergoing transition to addiction (Addict-like). Dysfunctions in prefrontal cortex (PFC) synaptic circuits are thought to be responsible for the loss of control over drug taking that characterizes addicted individuals. Here, we studied the synaptic alterations in prelimbic PFC (pPFC) circuits associated with transition to addiction. We discovered that some of the changes induced by cocaine self-administration (SA), such as the impairment of the endocannabinoid-mediated long-term synaptic depression (eCB-LTD) was similarly abolished in Non-Addict- and Addict-like rats and thus unrelated to transition to addiction. In contrast, metabotropic glutamate receptor 2/3-mediated LTD (mGluR2/3-LTD) was specifically suppressed in Addict-like rats, which also show a concomitant postsynaptic plasticity expressed as a change in the relative contribution of AMPAR and NMDAR to basal glutamate-mediated synaptic transmission. Addiction-associated synaptic alterations in the pPFC were not fully developed at early stages of cocaine SA, when addiction-like behaviors are still absent, suggesting that pathological behaviors appear once the pPFC is compromised. These data identify specific synaptic impairments in the pPFC associated with addiction and support the idea that alterations of synaptic plasticity are core markers of drug dependence.
authors.affiliation: INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, Bordeaux, France.
authors.forename: F
authors.initials: F
authors.lastname: Kasanetz
authors.forename: M
authors.initials: M
authors.lastname: Lafourcade
authors.forename: V
authors.initials: V
authors.lastname: Deroche-Gamonet
authors.forename: J-M
authors.initials: JM
authors.lastname: Revest
authors.forename: N
authors.initials: N
authors.lastname: Berson
authors.forename: E
authors.initials: E
authors.lastname: Balado
authors.forename: J-F
authors.initials: JF
authors.lastname: Fiancette
authors.forename: P
authors.initials: P
authors.lastname: Renault
authors.forename: P-V
authors.initials: PV
authors.lastname: Piazza
authors.forename: O J
authors.initials: OJ
authors.lastname: Manzoni
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012646:Self Administration; D019966:Substance-Related Disorders / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018765:Dopamine Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; C118218:LY 379268; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D003042:Cocaine