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Background <p>C57BL/6 and DBA/2 mouse strains differ markedly in behavioral responses to acute and chronic morphine administration. Some of these disparities might be underlain by and/or correlated with different expression of the opioid propeptide genes <i>Pdyn</i> and <i>Penk</i>. The objective of our study was to characterize the influence of morphine on <i>Pdyn</i> and <i>Penk</i> expression in substance abuse-related forebrain regions of C57BL/6 and DBA/2 mice.</p> Methods <p><i>Pdyn</i> and <i>Penk</i> mRNA levels were measured using in situ hybridization after acute or chronic morphine administration, and during 24–48-h withdrawal.</p> Results <p><i>Pdyn</i> and <i>Penk</i> gene expression was increased after chronic morphine and throughout withdrawal in all investigated brain regions. The changes were strain-specific in the central amygdaloid nucleus (CeA), where both genes were upregulated exclusively in C57BL/6 mice. The effect of morphine on <i>Penk</i> and <i>Pdyn</i> mRNA levels in the NAc core and shell did not significantly differ between the strains. However, trends within the data suggest greater upregulation of <i>Pdyn</i> in DBA/2 mice and of <i>Penk</i> in C57BL/6 mice. No such trends were observed in the dorsal striatum.</p> Conclusions <p>Our results suggest that <i>Penk</i>-expressing neurons of the CeA, which are critical for some withdrawal symptoms, adapt differently to chronic morphine in C57BL/6 vs. DBA/2 mice. We discuss how this may correspond to the inter-strain disparity in the opioid withdrawal syndrome intensity. We also analyze possible causes and consequences of the presumed inter-strain differences in morphine effects within the NAc.</p>

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The influence of morphine treatment on the opioid propeptide gene expression in the forebrain of two inbred mouse strains with different sensitivity to opioids

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  • 发表日期：

    2025年8月14日

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  • Barbara Ziółkowska,
  • Agnieszka Gieryk,
  • Ryszard Przewłocki

摘要

Background

C57BL/6 and DBA/2 mouse strains differ markedly in behavioral responses to acute and chronic morphine administration. Some of these disparities might be underlain by and/or correlated with different expression of the opioid propeptide genes Pdyn and Penk. The objective of our study was to characterize the influence of morphine on Pdyn and Penk expression in substance abuse-related forebrain regions of C57BL/6 and DBA/2 mice.

Methods

Pdyn and Penk mRNA levels were measured using in situ hybridization after acute or chronic morphine administration, and during 24–48-h withdrawal.

Results

Pdyn and Penk gene expression was increased after chronic morphine and throughout withdrawal in all investigated brain regions. The changes were strain-specific in the central amygdaloid nucleus (CeA), where both genes were upregulated exclusively in C57BL/6 mice. The effect of morphine on Penk and Pdyn mRNA levels in the NAc core and shell did not significantly differ between the strains. However, trends within the data suggest greater upregulation of Pdyn in DBA/2 mice and of Penk in C57BL/6 mice. No such trends were observed in the dorsal striatum.

Conclusions

Our results suggest that Penk-expressing neurons of the CeA, which are critical for some withdrawal symptoms, adapt differently to chronic morphine in C57BL/6 vs. DBA/2 mice. We discuss how this may correspond to the inter-strain disparity in the opioid withdrawal syndrome intensity. We also analyze possible causes and consequences of the presumed inter-strain differences in morphine effects within the NAc.