DESCRIPTION:

The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. 

LABEL:

Fentanyl_C57BL/6 J _A/J_nucleus accumbens_bySex_Log2FC

SCORE TYPE:

Effect

DATE ADDED:

2024-01-02

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman

TITLE:

Fentanyl-induced acute and conditioned behaviors in two inbred mouse lines: Potential role for Glyoxalase.

JOURNAL:

Physiology & behavior Jan 2022, Vol 243, pp. 113630

ABSTRACT:

An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake. PUBMED: 34710466
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