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Knockdown of tropomyosin‐related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress‐induced cross‐sensitization to amphetamine in rats
Author(s) -
Wang Junshi,
Bina Robert W.,
Wingard Jeffrey C.,
Terwilliger Ernest F.,
Hammer Ronald P.,
Nikulina Ella M.
Publication year - 2014
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12464
Subject(s) - nucleus accumbens , tropomyosin receptor kinase b , social defeat , ventral tegmental area , brain derived neurotrophic factor , neurotrophic factors , sensitization , ampa receptor , gene knockdown , chemistry , amphetamine , synapsin i , pharmacology , medicine , glutamate receptor , neuroscience , biology , receptor , dopamine , biochemistry , apoptosis , dopaminergic , vesicle , membrane , synaptic vesicle
Abstract The nucleus accumbens ( NA c) is a critical brain region for the rewarding effects of drugs of abuse. Brain‐derived neurotrophic factor ( BDNF ) can facilitate stress‐ and drug‐induced neuroadaptation in the mesocorticolimbic system. BDNF ‐containing projections to the NA c originate from the ventral tegmental area ( VTA ) and the prefrontal cortex, and BDNF release activates tropomyosin‐related kinase B ( T rk B ). In this study, we examined the necessity for BDNF ‐ T rk B signaling in the NA c shell during social defeat stress‐induced cross‐sensitization to amphetamine. Adeno‐associated virus expressing short hairpin RNA directed against T rk B ( AAV ‐sh T rk B ) was infused bilaterally into the NA c shell to knock down T rk B , whereas AAV ‐ GFP (green fluorescent protein) was used as the control virus. Rats were exposed to intermittent social defeat stress or handling procedures; amphetamine challenge was given at 10 days after the last defeat and locomotor activity was measured. Stressed rats that received the control virus showed cross‐sensitization to amphetamine compared with the handled rats. In contrast, NA c T rk B knockdown prevented social defeat stress‐induced cross‐sensitization. T rk B knockdown in the NA c was found to reduce the level of phospho‐extracellular signal‐regulated kinase 1 in this region. NA c T rk B knockdown also prevented stress‐induced elevation of BDNF and the glutamate receptor type 1 (GluA1) subunit of AMPA receptor in the VTA , as well as Δ F os B expression in the NA c. These findings indicated that BDNF ‐ T rk B signaling in the NA c shell was required for social defeat stress‐induced cross‐sensitization. NA c T rk B ‐ BDNF signaling also appeared to be involved in the regulation of GluA1 in the VTA , as well as in the NA c Δ F os B accumulation that could trigger cross‐sensitization after social defeat stress.