renatal Cannabis Exposure Increases Heroin Seeking ith Allostatic Changes in Limbic Enkephalin Systems n Adulthood

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