Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood.
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 Delta(9)-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 mu 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.
Spano
M Sabrina
MS
Karolinska Institute, Department of Clinical Neuroscience, Psychiatry Section, S-17176 Stockholm, Sweden.
Ellgren
Maria
M
Wang
X
X
Hurd
Yasmin L
YL
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D002188:Cannabis; D003216:Conditioning, Operant / Q000187:drug effects; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006556:Heroin Dependence / Q000209:etiology*; D017403:In Situ Hybridization / Q000379:methods; D008032:Limbic System / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D011485:Protein Binding / Q000187:drug effects; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects
D004745:Enkephalins; D011498:Protein Precursors; C036448:pre-prodynorphin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004399:Dynorphins