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.

The European Journal of Neuroscience
Junshi WangElla M Nikulina

Abstract

The nucleus accumbens (NAc) 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 NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB). In this study, we examined the necessity for BDNF-TrkB signaling in the NAc shell during social defeat stress-induced cross-sensitization to amphetamine. Adeno-associated virus expressing short hairpin RNA directed against TrkB (AAV-shTrkB) was infused bilaterally into the NAc shell to knock down TrkB, 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, NAc TrkB knockdown prevented social defeat stress-induced cross-sensitization. TrkB knockdown in the NAc was found to reduce the level of phospho-...Continue Reading

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Citations

Oct 4, 2015·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Maurice Y F ShenSusan R George
May 3, 2019·Psychopharmacology·M Carmen Blanco-GandiaMarta Rodríguez-Arias

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