CaMKII activity in the ventral tegmental area gates cocaine-induced synaptic plasticity in the nucleus accumbens. Neuropsychopharmacology 2014 Mar;39(4):989-99
Date
10/25/2013Pubmed ID
24154664Pubmed Central ID
PMC3924533DOI
10.1038/npp.2013.299Scopus ID
2-s2.0-84894088141 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
Addictive drugs such as cocaine induce synaptic plasticity in discrete regions of the reward circuit. The aim of the present study is to investigate whether cocaine-evoked synaptic plasticity in the ventral tegmental area (VTA) and nucleus accumbens (NAc) is causally linked. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of long-term synaptic plasticity, learning, and drug addiction. We examined whether blocking CaMKII activity in the VTA affected cocaine conditioned place preference (CPP) and cocaine-evoked synaptic plasticity in its target brain region, the NAc. TatCN21 is a CaMKII inhibitory peptide that blocks both stimulated and autonomous CaMKII activity with high selectivity. We report that intra-VTA microinjections of tatCN21 before cocaine conditioning blocked the acquisition of cocaine CPP, whereas intra-VTA microinjections of tatCN21 before saline conditioning did not significantly affect cocaine CPP, suggesting that the CaMKII inhibitor blocks cocaine CPP through selective disruption of cocaine-cue-associated learning. Intra-VTA tatCN21 before cocaine conditioning blocked cocaine-evoked depression of excitatory synaptic transmission in the shell of the NAc slices ex vivo. In contrast, intra-VTA microinjection of tatCN21 just before the CPP test did not affect the expression of cocaine CPP and cocaine-induced synaptic plasticity in the NAc shell. These results suggest that CaMKII activity in the VTA governs cocaine-evoked synaptic plasticity in the NAc during the time window of cocaine conditioning.
Author List
Liu X, Liu Y, Zhong P, Wilkinson B, Qi J, Olsen CM, Bayer KU, Liu QSAuthors
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinChristopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2
Cocaine
Conditioning, Operant
Dopamine Uptake Inhibitors
Dose-Response Relationship, Drug
Drug Administration Schedule
Enzyme Inhibitors
Excitatory Amino Acid Agonists
Male
N-Methylaspartate
Neural Pathways
Neuronal Plasticity
Nucleus Accumbens
Rats
Rats, Sprague-Dawley
Time Factors
Ventral Tegmental Area
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
