Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.

Autor:	Kawa AB; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239., Hashimoto JG; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239.; VA Portland Health Care System, Portland, OR 97239., Beutler MM; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239., Guizzetti M; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239.; VA Portland Health Care System, Portland, OR 97239., Wolf ME; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 16. Date of Electronic Publication: 2024 Sep 16.
DOI:	10.1101/2024.09.15.613147
Abstrakt:	In the 'incubation of cocaine craving' model of relapse, rats exhibit progressive intensification (incubation) of cue-induced craving over several weeks of forced abstinence from cocaine self-administration. The expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens core (NAcC) medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity and the expression of incubation depends on ongoing protein translation, and the regulation of translation is altered after incubation of cocaine craving. Here we used male and female rats that express Cre recombinase in either dopamine D1 receptor- or adenosine 2a (A2a) receptor-expressing MSN to express a GFP-tagged ribosomal protein in a cell-type specific manner, enabling us to use Translating Ribosome Affinity Purification (TRAP) to isolate actively translating mRNAs from both MSN subtypes for analysis by RNA-seq. We compared rats that self-administered saline or cocaine. Saline rats were assessed on abstinence day (AD) 1, while cocaine rats were assessed on AD1 or AD40-50. For both D1-MSN and A2a-MSN, there were few differentially translated genes between saline and cocaine AD1 groups. In contrast, pronounced differences in the translatome were observed between cocaine rats on AD1 and AD40-50, and this was far more robust in D1-MSN. Notably, all comparisons revealed sex differences in translating mRNAs. Sequencing results were validated by qRT-PCR for several genes of interest. This study, the first to combine TRAP-seq, transgenic rats, and a cocaine self-administration paradigm, identifies translating mRNAs linked to incubation of cocaine craving in D1-MSN and A2a-MSN of the NAcC. Competing Interests: Competing Interests: The authors have nothing to disclose.
Databáze:	MEDLINE
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