Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood

M. Sabrina Spano, Maria Ellgren, X. Wang, Yasmin L. Hurd

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Background: Prenatal cannabis exposure is a growing concern with little known about the long-term consequences on behavior and neural systems relevant for reward and emotional processing. Methods: We used an animal model to study the effects of prenatal exposure to Δ9-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult males (postnatal day 62). Rats were exposed to THC (.15 mg/kg) or vehicle from gestational day 5 to postnatal day 2. Results: Both pretreatment groups showed similar heroin intake, but THC-exposed rats exhibited shorter latency to the first active lever press, responded more for low heroin doses, and had higher heroin-seeking during mild stress and drug extinction. THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but was elevated in adulthood; no adult striatal changes on preprodynorphin mRNA or PENK in caudate-putamen. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. THC animals had reduced heroin-induced locomotor activity and nucleus accumbens μ opioid receptor coupling. Conclusions: This study demonstrates enduring effects of prenatal THC exposure into adulthood that is evident on heroin-seeking behavior during extinction and allostatic changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress response.

Original languageEnglish
Pages (from-to)554-563
Number of pages10
JournalBiological Psychiatry
Issue number4
StatePublished - 15 Feb 2007
Externally publishedYes


  • CB
  • Cannabinoid receptor
  • G protein-coupling
  • extended amygdala
  • locomotor activity
  • opioid neuropeptide
  • rimonabant


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