{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T12:43:48Z","timestamp":1794055428390,"version":"4.8.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg\/kg morphine (1 mg\/kg increment per week), (3) 7 mg\/kg methadone, and (4) 3 mg\/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher mortality and much less sensitivity to morphine-induced antinociception than prenatal exposure to morphine or methadone. This indicates that buprenorphine in higher doses may not be an ideal maintenance drug for treating pregnant women. This study provides a reference in selecting doses for clinical usage in treating pregnant heroin addicts.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1423-0127-17-46","type":"journal-article","created":{"date-parts":[[2010,6,8]],"date-time":"2010-06-08T06:16:09Z","timestamp":1275977769000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine"],"prefix":"10.1186","volume":"17","author":[{"given":"Yao-Chang","family":"Chiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsai-Wei","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Wei-Sheng","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Ying","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ing-Kang","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,6,7]]},"reference":[{"key":"160_CR1","unstructured":"Results from the 2007 National Survey on Drug Use and Health: National Findings. [http:\/\/www.oas.samhsa.gov\/nsduh\/2k7nsduh\/2k7Results.pdf]"},{"key":"160_CR2","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1542\/peds.100.1.79","volume":"100","author":"EM Ostrea Jr","year":"1997","unstructured":"Ostrea EM, Ostrea AR, Simpson PM: Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Pediatrics. 1997, 100: 79-83. 10.1542\/peds.100.1.79.","journal-title":"Pediatrics"},{"key":"160_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1017\/S1461145703003523","volume":"6","author":"J Yanai","year":"2003","unstructured":"Yanai J, Huleihel R, Izrael M, Metsuyanim S, Shahak H, Vatury O, Yaniv SP: Functional changes after prenatal opiate exposure related to opiate receptors' regulated alterations in cholinergic innervation. Int J Neuropsychopharmacol. 2003, 6: 253-265. 10.1017\/S1461145703003523.","journal-title":"Int J Neuropsychopharmacol"},{"key":"160_CR4","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0378-4274(02)00505-2","volume":"140-141","author":"A Ornoy","year":"2003","unstructured":"Ornoy A: The impact of intrauterine exposure versus postnatal environment in neurodevelopmental toxicity: long-term neurobehavioral studies in children at risk for developmental disorders. Toxicol Lett. 2003, 140-141: 171-181. 10.1016\/S0378-4274(02)00505-2.","journal-title":"Toxicol Lett"},{"key":"160_CR5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1365-2214.2007.00768.x","volume":"34","author":"J Topley","year":"2008","unstructured":"Topley J, Windsor D, Williams R: Behavioural, developmental and child protection outcomes following exposure to Class A drugs in pregnancy. Child Care Health Dev. 2008, 34: 71-76.","journal-title":"Child Care Health Dev"},{"key":"160_CR6","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0022-3476(79)80107-9","volume":"63","author":"GS Wilson","year":"1979","unstructured":"Wilson GS, McCreary R, Kean J, Baxter JC: The development of preschool children of heroin-addicted mothers: a controlled study. Pediatrics. 1979, 63: 135-141.","journal-title":"Pediatrics"},{"key":"160_CR7","doi-asserted-by":"crossref","first-page":"S133","DOI":"10.36076\/ppj.2008\/11\/S133","volume":"11","author":"AM Trescot","year":"2008","unstructured":"Trescot AM, Datta S, Lee M, Hansen H: Opioid pharmacology. Pain Physician. 2008, 11: S133-153.","journal-title":"Pain Physician"},{"key":"160_CR8","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1111\/j.1751-486X.2007.00243.x","volume":"11","author":"UA Pritham","year":"2007","unstructured":"Pritham UA, Troese M, Stetson A: Methadone and buprenorphine treatment during pregnancy: what are the effects on infants?. Nurs Womens Health. 2007, 11: 558-567. 10.1111\/j.1751-486X.2007.00243.x.","journal-title":"Nurs Womens Health"},{"key":"160_CR9","first-page":"347","volume":"67","author":"H Joseph","year":"2000","unstructured":"Joseph H, Stancliff S, Langrod J: Methadone maintenance treatment (MMT): a review of historical and clinical issues. Mt Sinai J Med. 2000, 67: 347-364.","journal-title":"Mt Sinai J Med"},{"key":"160_CR10","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/j.1479-828X.2004.00221.x","volume":"44","author":"JP Ludlow","year":"2004","unstructured":"Ludlow JP, Evans SF, Hulse G: Obstetric and perinatal outcomes in pregnancies associated with illicit substance abuse. Aust N Z J Obstet Gynaecol. 2004, 44: 302-306. 10.1111\/j.1479-828X.2004.00221.x.","journal-title":"Aust N Z J Obstet Gynaecol"},{"key":"160_CR11","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/j.1471-0528.2008.02073.x","volume":"116","author":"C Dryden","year":"2009","unstructured":"Dryden C, Young D, Hepburn M, Mactier H: Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources. BJOG. 2009, 116: 665-671. 10.1111\/j.1471-0528.2008.02073.x.","journal-title":"BJOG"},{"key":"160_CR12","doi-asserted-by":"publisher","first-page":"395","DOI":"10.2174\/1570159043359477","volume":"2","author":"K Lutfy","year":"2004","unstructured":"Lutfy K, Cowan A: Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004, 2: 395-402. 10.2174\/1570159043359477.","journal-title":"Curr Neuropharmacol"},{"key":"160_CR13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0022-3565(25)33306-9","volume":"223","author":"W Sadee","year":"1982","unstructured":"Sadee W, Rosenbaum JS, Herz A: Buprenorphine: differential interaction with opiate receptor subtypes in vivo. J Pharmacol Exp Ther. 1982, 223: 157-162.","journal-title":"J Pharmacol Exp Ther"},{"key":"160_CR14","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.ejogrb.2008.10.012","volume":"142","author":"L Simmat-Durand","year":"2009","unstructured":"Simmat-Durand L, Lejeune C, Gourarier L: Pregnancy under high-dose buprenorphine. Eur J Obstet Gynecol Reprod Biol. 2009, 142: 119-123.","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"160_CR15","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1053\/beog.2001.0242","volume":"15","author":"A Wright","year":"2001","unstructured":"Wright A, Walker J: Drugs of abuse in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2001, 15: 987-998. 10.1053\/beog.2001.0242.","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"160_CR16","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1002\/glia.20675","volume":"56","author":"ES Sanchez","year":"2008","unstructured":"Sanchez ES, Bigbee JW, Fobbs W, Robinson SE, Sato-Bigbee C: Opioid addiction and pregnancy: perinatal exposure to buprenorphine affects myelination in the developing brain. Glia. 2008, 56: 1017-1027. 10.1002\/glia.20675.","journal-title":"Glia"},{"key":"160_CR17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/00001756-200302100-00016","volume":"14","author":"LC Chiou","year":"2003","unstructured":"Chiou LC, Yeh GC, Fan SH, How CH, Chuang KC, Tao PL: Prenatal morphine exposure decreases analgesia but not K+ channel activation. Neuroreport. 2003, 14: 239-242. 10.1097\/00001756-200302100-00016.","journal-title":"Neuroreport"},{"key":"160_CR18","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0022-3565(25)30537-9","volume":"197","author":"JP O'Callaghan","year":"1976","unstructured":"O'Callaghan JP, Holtzman SG: Prenatal administration of morphine to the rat: tolerance to the analgesic effect of morphine in the offspring. J Pharmacol Exp Ther. 1976, 197: 533-544.","journal-title":"J Pharmacol Exp Ther"},{"key":"160_CR19","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1016\/S0024-3205(01)01316-9","volume":"69","author":"PL Tao","year":"2001","unstructured":"Tao PL, Yeh GC, Su CH, Wu YH: Co-administration of dextromethorphan during pregnancy and throughout lactation significantly decreases the adverse effects associated with chronic morphine administration in rat offspring. Life Sci. 2001, 69: 2439-2450. 10.1016\/S0024-3205(01)01316-9.","journal-title":"Life Sci"},{"key":"160_CR20","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0022-3565(24)29441-6","volume":"298","author":"SE Robinson","year":"2001","unstructured":"Robinson SE, Wallace MJ: Effect of perinatal buprenorphine exposure on development in the rat. J Pharmacol Exp Ther. 2001, 298: 797-804.","journal-title":"J Pharmacol Exp Ther"},{"key":"160_CR21","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1097\/00000542-200703000-00022","volume":"106","author":"JR Holtman Jr","year":"2007","unstructured":"Holtman JR, Wala EP: Characterization of the antinociceptive and pronociceptive effects of methadone in rats. Anesthesiology. 2007, 106: 563-571. 10.1097\/00000542-200703000-00022.","journal-title":"Anesthesiology"},{"key":"160_CR22","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1111\/j.1476-5381.1977.tb07532.x","volume":"60","author":"A Cowan","year":"1977","unstructured":"Cowan A, Lewis JW, Macfarlane IR: Agonist and antagonist properties of buprenorphine, a new antinociceptive agent. Br J Pharmacol. 1977, 60: 537-545.","journal-title":"Br J Pharmacol"},{"key":"160_CR23","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s11373-008-9252-0","volume":"15","author":"X Dai","year":"2008","unstructured":"Dai X, Brunson CD, Rockhold RW, Loh HH, Ho IK, Ma T: Gender differences in the antinociceptive effect of tramadol, alone or in combination with gabapentin, in mice. J Biomed Sci. 2008, 15: 645-651. 10.1007\/s11373-008-9252-0.","journal-title":"J Biomed Sci"},{"key":"160_CR24","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/0091-3057(82)90113-7","volume":"17","author":"ML Kirby","year":"1982","unstructured":"Kirby ML, DeRossett SE, Holtzman SG: Enhanced analgesic response to morphine in adult rats exposed to morphine prenatally. Pharmacol Biochem Behav. 1982, 17: 1161-1164. 10.1016\/0091-3057(82)90113-7.","journal-title":"Pharmacol Biochem Behav"},{"key":"160_CR25","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/0892-0362(94)00079-S","volume":"17","author":"DE Hutchings","year":"1995","unstructured":"Hutchings DE, Zmitrovich AC, Hamowy AS, Liu PY: Prenatal administration of buprenorphine using the osmotic minipump: a preliminary study of maternal and offspring toxicity and growth in the rat. Neurotoxicol Teratol. 1995, 17: 419-423. 10.1016\/0892-0362(94)00079-S.","journal-title":"Neurotoxicol Teratol"},{"key":"160_CR26","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0091-3057(96)00278-X","volume":"55","author":"R Gagin","year":"1996","unstructured":"Gagin R, Cohen E, Shavit Y: Prenatal exposure to morphine alters analgesic responses and preference for sweet solutions in adult rats. Pharmacol Biochem Behav. 1996, 55: 629-634. 10.1016\/S0091-3057(96)00278-X.","journal-title":"Pharmacol Biochem Behav"},{"key":"160_CR27","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1016\/j.lfs.2005.07.023","volume":"78","author":"R Bhat","year":"2006","unstructured":"Bhat R, Chari G, Rao R: Effects of prenatal cocaine, morphine, or both on postnatal opioid (mu) receptor development. Life Sci. 2006, 78: 1478-1482. 10.1016\/j.lfs.2005.07.023.","journal-title":"Life Sci"},{"key":"160_CR28","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/0006-8993(95)00638-7","volume":"690","author":"A Rimanoczy","year":"1995","unstructured":"Rimanoczy A, Vathy I: Prenatal exposure to morphine alters brain mu opioid receptor characteristics in rats. Brain Res. 1995, 690: 245-248. 10.1016\/0006-8993(95)00638-7.","journal-title":"Brain Res"},{"key":"160_CR29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0922-4106(91)90059-Q","volume":"208","author":"TJ De Vries","year":"1991","unstructured":"De Vries TJ, Van Vliet BJ, Hogenboom F, Wardeh G, Van der Laan JW, Mulder AH, Schoffelmeer AN: Effect of chronic prenatal morphine treatment of mu-opioid receptor-regulated adenylate cyclase activity and neurotransmitter release in rat brain slices. Eur J Pharmacol. 1991, 208: 97-104. 10.1016\/0922-4106(91)90059-Q.","journal-title":"Eur J Pharmacol"},{"key":"160_CR30","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/0165-3806(92)90113-B","volume":"70","author":"R Basheer","year":"1992","unstructured":"Basheer R, Yang J, Tempel A: Chronic prenatal morphine treatment decreases G alpha s mRNA levels in neonatal frontal cortex. Brain Res Dev Brain Res. 1992, 70: 145-148. 10.1016\/0165-3806(92)90113-B.","journal-title":"Brain Res Dev Brain Res"},{"key":"160_CR31","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/0169-328X(95)00127-E","volume":"33","author":"A Tempel","year":"1995","unstructured":"Tempel A, Yang J, Basheer R: Prenatal morphine exposure differentially alters expression of opioid peptides in striatum of newborns. Brain Res Mol Brain Res. 1995, 33: 227-232. 10.1016\/0169-328X(95)00127-E.","journal-title":"Brain Res Mol Brain Res"},{"key":"160_CR32","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/S0278-5846(02)00355-X","volume":"27","author":"I Vathy","year":"2003","unstructured":"Vathy I, Slamberova R, Rimanoczy A, Riley MA, Bar N: Autoradiographic evidence that prenatal morphine exposure sex-dependently alters mu-opioid receptor densities in brain regions that are involved in the control of drug abuse and other motivated behaviors. Prog Neuropsychopharmacol Biol Psychiatry. 2003, 27: 381-393. 10.1016\/S0278-5846(02)00355-X.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"160_CR33","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/0024-3205(81)90202-2","volume":"29","author":"IS Zagon","year":"1981","unstructured":"Zagon IS, McLaughlin PJ: Enhanced sensitivity to methadone in adult rats perinatally exposed to methadone. Life Sci. 1981, 29: 1137-1142. 10.1016\/0024-3205(81)90202-2.","journal-title":"Life Sci"},{"key":"160_CR34","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jpain.2008.09.011","volume":"10","author":"L He","year":"2009","unstructured":"He L, Kim J, Ou C, McFadden W, van Rijn RM, Whistler JL: Methadone antinociception is dependent on peripheral opioid receptors. J Pain. 2009, 10: 369-379. 10.1016\/j.jpain.2008.09.011.","journal-title":"J Pain"},{"key":"160_CR35","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/S0022-3565(24)38234-5","volume":"289","author":"AM Davis","year":"1999","unstructured":"Davis AM, Inturrisi CE: d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia. J Pharmacol Exp Ther. 1999, 289: 1048-1053.","journal-title":"J Pharmacol Exp Ther"},{"key":"160_CR36","first-page":"399","volume":"8","author":"C Wang","year":"1986","unstructured":"Wang C, Pasulka P, Perry B, Pizzi WJ, Schnoll SH: Effect of perinatal exposure to methadone on brain opioid and alpha 2-adrenergic receptors. Neurobehav Toxicol Teratol. 1986, 8: 399-402.","journal-title":"Neurobehav Toxicol Teratol"},{"key":"160_CR37","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/0892-0362(92)90006-V","volume":"14","author":"NA Darmani","year":"1992","unstructured":"Darmani NA, Schnoll SH, Pandey U, Martin BR: Chronic prenatal methadone exposure alters central opioid mu-receptor affinity in both fetal and maternal brain. Neurotoxicol Teratol. 1992, 14: 265-271. 10.1016\/0892-0362(92)90006-V.","journal-title":"Neurotoxicol Teratol"},{"key":"160_CR38","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00213-006-0365-8","volume":"186","author":"G Grecksch","year":"2006","unstructured":"Grecksch G, Bartzsch K, Widera A, Becker A, Hollt V, Koch T: Development of tolerance and sensitization to different opioid agonists in rats. Psychopharmacology (Berl). 2006, 186: 177-184. 10.1007\/s00213-006-0365-8.","journal-title":"Psychopharmacology (Berl)"},{"key":"160_CR39","doi-asserted-by":"crossref","first-page":"10331","DOI":"10.1523\/JNEUROSCI.23-32-10331.2003","volume":"23","author":"K Lutfy","year":"2003","unstructured":"Lutfy K, Eitan S, Bryant CD, Yang YC, Saliminejad N, Walwyn W, Kieffer BL, Takeshima H, Carroll FI, Maidment NT, Evans CJ: Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci. 2003, 23: 10331-10337.","journal-title":"J Neurosci"},{"key":"160_CR40","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s002130000620","volume":"154","author":"EA Walker","year":"2001","unstructured":"Walker EA, Young AM: Differential tolerance to antinociceptive effects of mu opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats. Psychopharmacology (Berl). 2001, 154: 131-142. 10.1007\/s002130000620.","journal-title":"Psychopharmacology (Berl)"},{"key":"160_CR41","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s00213-008-1112-0","volume":"198","author":"EM Glover","year":"2008","unstructured":"Glover EM, Davis M: Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone. Psychopharmacology (Berl). 2008, 198: 167-180. 10.1007\/s00213-008-1112-0.","journal-title":"Psychopharmacology (Berl)"},{"key":"160_CR42","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/0165-3806(94)90100-7","volume":"80","author":"MM Belcheva","year":"1994","unstructured":"Belcheva MM, Dawn S, Barg J, McHale RJ, Ho MT, Ignatova E, Coscia CJ: Transient down-regulation of neonatal rat brain mu-opioid receptors upon in utero exposure to buprenorphine. Brain Res Dev Brain Res. 1994, 80: 158-162. 10.1016\/0165-3806(94)90100-7.","journal-title":"Brain Res Dev Brain Res"},{"key":"160_CR43","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/S0165-3806(98)00117-5","volume":"111","author":"MM Belcheva","year":"1998","unstructured":"Belcheva MM, Bohn LM, Ho MT, Johnson FE, Yanai J, Barron S, Coscia CJ: Brain opioid receptor adaptation and expression after prenatal exposure to buprenorphine. Brain Res Dev Brain Res. 1998, 111: 35-42. 10.1016\/S0165-3806(98)00117-5.","journal-title":"Brain Res Dev Brain Res"},{"key":"160_CR44","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0891-0618(01)00135-1","volume":"22","author":"CR Neal Jr","year":"2001","unstructured":"Neal CR, Akil H, Watson SJ: Expression of orphanin FQ and the opioid receptor-like (ORL1) receptor in the developing human and rat brain. J Chem Neuroanat. 2001, 22: 219-249. 10.1016\/S0891-0618(01)00135-1.","journal-title":"J Chem Neuroanat"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1423-0127-17-46.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:14:22Z","timestamp":1740165262000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/1423-0127-17-46"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,7]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["160"],"URL":"https:\/\/doi.org\/10.1186\/1423-0127-17-46","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,7]]},"assertion":[{"value":"1 April 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"46"}}