Near-term fetuses of different mammalian species, including humans, exhibit functional sensory and learning capabilities. The neurobiological literature indicates that the unborn organism processes sensory stimuli present in the amniotic fluid, retains this information for considerable amounts of time, and is also capable of associating such stimuli with biologically relevant events. This research has stimulated studies aimed at the analysis of fetal and neonatal learning about ethanol, a topic that constitutes the core of the present review. Ethanol has characteristic sensory (olfactory, taste, and trigeminal) attributes and can exert pharmacologic reinforcing effects. The studies under examination support the hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol. These levels of prenatal ethanol exposure do not generate evident morphologic or neurobehavioral alterations in the offspring, but they exert a significant impact upon later ethanol-seeking and intake behaviors. Supported by preclinical and clinical findings, this review contributes to strengthening the case for the ability of prenatal ethanol exposure to have effects on the postnatal organism.
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References
1.
Spear NE, Molina JC. Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review. Alcohol Clin Exp Res29:909–929, 2005.
2.
Cudd TA. Animal model systems for the study of alcohol teratology. Exp Biol Med (Maywood)230:389–393, 2005.
3.
Roebuck TM, Mattson SN, Riley EP. Prenatal exposure to alcohol: effects on brain structure and neuropsychological functioning. In: Hannigan JH, Spear LP, Spear NE, Goodlett CR, Eds. Alcohol and Alcoholism: Effects on Brain and Development. Hillsdale, NJ: Lawrence Erlbaum Associates, pp1–16, 1999.
4.
Riley EP, McGee CL. Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior. Exp Biol Med230: 357–365, 2005.
5.
West JR. Recent findings on the mechanisms by which alcohol damages the developing nervous system. Alcohol Alcohol (Suppl 2): 395–399, 1994.
6.
Faas AE, Spontón ED, Moya PR, Molina JC. Differential responsiveness to alcohol odor in human neonates: effects of maternal consumption during gestation. Alcohol22:7–17, 2000.
7.
Dawson DA, Grant BF, Chow PS. Gender differences in alcohol intake. In: Hunt WA, Zahkari S, Eds. Stress Gender and Alcohol-Seeking Behavior. Bethesda, MD: National Institute of Alcohol Abuse and Alcoholism Research, pp3–121, 1995.
8.
Scher MS, Richardson GA, Robles N, Geva D, Goldschmidt L, Dahl RE, Sclabassi RJ, Day NL. Effects of prenatal substance: altered maturation of visual evoked potentials. Pediatr Neurol18:236–243, 1998.
9.
Thompson RF, Spencer WA. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev73:16–43, 1966.
10.
Faas AE. Estudios funcionales del sistema nervioso central del recién nacido. Aplicaciones del aprendizaje no asociativo en la evaluación neonatal. PhD thesis, Universidad Nacional de Cordoba, Argentina, 2001.
11.
Ekman P, Friesen W. Facial Action Coding System: A technique for measurement of facial movement. Palo Alto, CA: Consulting Psychologist Press, 1978.
12.
Hankin JR. Fetal alcohol syndrome prevention research. Alcohol Res Health26:58–65, 2002.
13.
Dillner L, Josefson D, Karcher H, Sheldon T, Dorozynski A, Zinn C. Alcohol—pushing the limits. BMJ312:7–9, 1996.
14.
Scher M, Richardson GA, Coble PA, Day NL, Stoffer DS. The effects of prenatal alcohol and marijuana exposure: disturbances in neonatal sleep cycling and arousal. Pediatr Res24:101–105, 1988.
15.
Chotro MG, Arias C. Exposure to low and moderate exposure of alcohol on late gestation modifies infantile response to and preference for alcohol in rats. Ann Ist Super Sanita42:22–30, 2006.
Dobbing J, Sands J. Quantitative growth and development of human brain. Arch Dis Child48:757–767, 1973.
18.
Dobbing J, Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev3:79–83, 1979.
19.
Lanier SA, Hayes JE, Duffy VB. Sweet and bitter tastes of alcoholic beverages mediate alcohol intake in of-age undergraduates. Physiol Behav17:821–831, 2005.
20.
Fifer WP, Moon CM. The effects of fetal experience with sound. In: Lecaunet JP, Fifer WP, Krasnegor N, Smotherman WP, Eds. Fetal Development: A Psychobiological Perspective. Hillsdale, NJ: Lawrence Erlbaum Associates, pp351–368, 1995.
21.
Pedersen PE, Blass EM. Prenatal and postnatal determinants of the 1st suckling episode in albino rats. Dev Psychobiol15:349–355, 1982.
22.
Ronca AE, Lamkin CA, Alberts JF. Maternal contributions to sensory experience in the fetal and newborn rat (Rattus norvigecus). J Comp Psychol107:61–74, 1993.
23.
Smotherman WP, Robinson SR. Behavior of rat fetuses following chemical or tactile stimulation. Behav Neurosci102:24–34, 1988.
24.
Smotherman WP, Robinson SR. The amniotic sac as scaffolding: prenatal ontogeny of an action pattern. Dev Psychobiol24:463–485, 1991.
25.
Alberts JF. Sensory-perceptual development in the Norway rat: a view toward comparative studies. In: Kail R, Spear NE, Eds. Comparative Perspectives on Memory Development. Hillsdale, NJ: Lawrence Erlbaum Associates, pp65–102, 1984.
26.
Ronca AE, Alberts JF. Sensory stimuli associated with gestation and parturition evoke cardiac and behavioral responses in the fetal rat. Dev Psychobiol55:270–282, 1994.
27.
Coppola DM, O’Connel RJ. Perinatal olfaction in the mouse: developmental morphology of the vomeronasal channel in preliminary 2-deoxyglucose studies in utero. In: Program of the 11th Meeting of the Association of Chemoreception Sciences (Achems XI) Sarasota, Florida, 1989.
28.
Coppola DM. The role of the main and accessory olfactory systems in prenatal olfaction. In: Marchlewska-Koj A, Lepri JJ, Müller-Schwarze D, Eds. Chemical Signals in Vertebrates (Vol. 9). New York: Plenum Press, pp189–196, 2001.
29.
Coppola DM, Millar LC. Stimulus access to the accessory olfactory system in the prenatal and perinatal rat. Neuroscience60:463–468, 1994.
30.
Coppola DM, Budde J, Millar L. The vomeronasal duct has a protracted postnatal development in the mouse. J Morphol218:59–64, 2005.
31.
Smotherman WP, Robinson SR. Rat fetuses respond to chemical stimuli in gas phase. Physiol Behav97:863–868, 1990.
32.
Smotherman WP, Robinson SR, Ronca AE, Alberts JF, Hepper P. Heart rate responses to the rat fetus and neonate to a chemosensory stimulus. Physiol Behav50:47–52, 1991.
33.
Smotherman WP. In utero chemosensory experience alters taste preferences and corticosterone responsiveness. Behav Neural Biol36: 61–68, 1982.
34.
Smotherman WP, Robinson SR. Habituation in the rat fetus. Q J Exp Psychol B44:215–230, 1992.
35.
Smotherman WP, Robinson SR. Habituation to chemosensory stimuli in the rat fetus: effects of endogenous kappa opioid activity. Behav Neurosci107:611–617, 1993.
36.
Smotherman WP. Odor aversion learning by the rat fetus. Physiol Behav29:769–771, 1982.
37.
Smotherman WP, Robinson SR. The rat fetus in its environment: behavioral adjustments to novel, familiar, aversive and conditioned stimuli presented in utero. Behav Neurosci99:521–530, 1985.
38.
Stikord G, Kimble DP, Smotherman WP. In utero taste/odor aversion conditioning in the rat. Physiol Behav28:5–7, 1982.
39.
Gruest N, Richer P, Hars B. Emergence of long-term memory for conditioned aversion in the rat fetus. Dev Psychobiol44:189–198, 2004.
40.
Mickley GA, Remmers-Roeber DR, Crouse C, Pelusso R. Ketamine blocks a taste-mediated conditioned motor response in perinatal rat. Pharmacol Biochem Behav66:547–552, 2000.
41.
Robinson SR, Hoeltzel TCM, Cooke KM, Umphress SM, Smotherman WP, Murrish DE. Oral capture and grasping of an artificial nipple by rat fetuses. Dev Psychobiol26:375–387, 1992.
42.
Petrov ES, Varlinskaya EI, Smotherman WP. Classical conditioning of responses to an artificial nipple in the rat fetus: mu and kappa opioid systems. Dev Psychobiol37:59–72, 2000.
43.
Arnold HM, Robinson SR, Spear NE, Smotherman WP. Conditioned opioid activity in the rat fetus. Behav Neurosci107:963–969, 1993.
44.
Schaal B, Coureaud G, Marlier L, Soussignan R. Fetal olfactory cognition preadapts neonatal behavior in mammals. In: Marchlewska-Koj A, Lepri JL, Muller-Schwarze, Eds. Chemical Signals in Vertebrates 9. New York: Kluwer Academic/Plenum Publishers, pp197–204, 2001.
45.
Schaal B, Hummel T, Soussignan R. Olfaction in the fetal and premature infant: functional status and clinical implications. Clin Perinatol31:261–285, 2004.
46.
Varendi H, Porter RH, Weimberg J. Attractiveness for amniotic fluid odor: evidence of prenatal learning? Acta Paediatr 85:1223–1227, 1996.
47.
Mennella JA, Beauchamp GK. The transfer of alcohol to human milk: effects on flavor and the infant’s behavior. N Engl J Med325:981–985, 1991.
48.
Mennella JA, Beauchamp GK. Early flavor experiences: when do they start? Nutr Today 29:25–31, 1994.
49.
Mennella JA. Mother’s milk: a medium for early flavor experiences. J Hum Lact11:39–45, 1995.
50.
Schaal B, Marlier L, Soussignan R. Responsiveness to the odour of amniotic fluid in the human neonate. Biol Neonate67:397–406, 1995.
51.
Schaal B, Marlier L, Soussignan R. Olfactory function in the human fetus: evidence from selective neonatal responsiveness to the odor of amniotic fluid. Behav Neurosci112:1438–1449, 1998.
52.
Schaal B, Soussignan R, Marlier L. Olfactory cognition at the start of life: the perinatal shaping of selective odor responsiveness. In: Rouby C, Schaal B, Dubois D, Gervais RB, Holley A, Eds. Olfaction, Taste, and Cognition. New York: Cambridge University Press, pp421–440, 2002.
53.
Varendi H, Christensson K, Porter RH, Wimberg J. Soothing effect of amniotic fluid smell in newborn infants. Early Hum Dev51:47–55, 1998.
54.
Varendi H, Porter RH, Winberg J. Natural odour preferences of newborn infants change over time. Acta Paediatr86:985–990, 1997.
55.
Marlier L, Schaal B, Soussignan R. Neonatal responsiveness to the odor of amniotic and lacteal fluids: a test of perinatal chemosensory continuity. Child Dev69:611–623, 1998.
56.
Marlier L, Schaal B. Human newborns prefer human milk: conspecific milk odor is attractive without postnatal experience. Child Dev76: 155–168, 2005.
57.
Schaal B, Orgeur P, Rognon C. Odor sensing in the human fetus: anatomical, functional and chemoecological bases. In: Lecaunet JP, Fifer WP, Krasnegor N, Smotherman WP, Eds. Fetal Development: A Psychobiological Perspective. Hillsdale, NJ: Lawrence Erlbaum Associates, pp205–238, 1995.
58.
Takami S, Yukimatsu M, Matsumura G, Nishiyama F. Vomeronasal epithelial cells of human fetuses contain immunoreactivity for G proteins, Goα and Giα2. Chem Senses26:517–522, 2001.
59.
Bilkó A, Altbäcker V, Hudson R. Transmission of food preference in the rabbit: the means of information transfer. Physiol Behav56:907–912, 1994.
60.
Semke E, Distel H, Hudson R. Specific enhancement of olfactory receptor sensitivity associated with fetal learning of food odors in the rabbit. Naturwissenschaften82:148–149, 1995.
Schaal B, Marlier L, Soussignan R. Human foetuses learn odours from their pregnant mother’s diet. Chem Senses25:729–737, 2000.
63.
Molina JC, Domínguez HD, López MF, Pepino MY, Faas AE. The role of fetal and infantile experience with alcohol in later recognition and acceptance patterns of the drug. In: Hanningan JH, Spear NE, Spear LP, Goodlett CR, Eds. Alcohol and Alcoholism: Brain and Development. Hillsdale, NJ: Lawrence Erlbaum Associates, pp199–228, 1999.
64.
Bannoura MD, Kraebel KS, Spear LP, Spear NE. Effects of preweanling ethanol odor exposure on ethanol preference. Alcohol15:213–217, 1998.
65.
Molina JC, Serwatka J, Spear NE. Changes in alcohol intake resulting from prior experience with alcohol odor in young rats. Pharmacol Biochem Behav21:387–391, 1984.
66.
Molina JC, Serwatka J, Spear NE. Alcohol drinking patterns of young adult rats as a function of infantile aversive experiences with alcohol odor. Behav Neural Biol46:257–271, 1986.
67.
Molina JC, Chotro MG, Spear NE. Early (preweanling) recognition of ethanol’s orosensory cues resulting from acute ethanol intoxication. Behav Neural Biol51:307–325, 1989.
Lopez MF, Molina JC. Chronic alcohol administration in the rat pup: effects upon later consumption of alcohol and other palatable solutions. Addict Biol4:169–180, 1999.
72.
Di Lorenzo P, Kiefer S, Rice A, García J. Neural and behavioral responsivity to ethyl alcohol as a tastant. Brain Res Bull3:55–61, 1986.
73.
Kiefer SW, Lawrence GJ. The sweet-bitter taste of alcohol: aversion generalization to various sweet-quinine mixtures in the rat. Chem Senses13:633–641, 1988.
74.
Kiefer SW, Mahadevan RS. The taste of alcohol for rats as revealed by aversion generalization tests. Chem Senses18:509–522, 1993.
75.
Molina JC, Chotro MG. Acute alcohol intoxication paired with appetitive reinforcement: effects upon ethanol intake in infant rats. Behav Neural Biol51:326–345, 1989.
76.
Molina JC, Chotro MG. Acute alcohol intoxication paired with aversive reinforcement: ethanol odor as a conditioned reinforcer in rat pups. Behav Neural Biol52:1–19, 1989.
77.
Molina JC, Serwatka J, Spear LP, Spear NE. Differential ethanol olfactory experiences affect ethanol ingestion in preweanlings but not in older rats. Behav Neural Biol44:90–100, 1985.
78.
Hunt PS, Kraebel KS, Rabine H, Spear LP, Spear NE. Enhanced ethanol intake in preweanling rats following exposure to ethanol in a nursing context. Dev Psychobiol26:133–153, 1993.
79.
Molina JC, Pepino MY, Johnson J, Spear NE. The infant rat learns about alcohol through interaction with an intoxicated mother. Alcohol Clin Exp Res24:428–437, 2000.
80.
Pepino MY, Kraebel KS, López MF, Spear NE, Molina JC. Behavioral detection of low concentrations of ethanol in the preweanling rat. Alcohol15:337–353, 1998.
81.
Pepino MY, Spear NE, Molina JC. Nursing experiences with an alcohol intoxicated dam counteracts appetitive conditioned responses towards alcohol. Alcohol Clin Exp Res25:18–24, 2001.
82.
Pepino MY, Abate P, Spear NE, Molina JC. Heightened ethanol intake in infant and adolescent rats following nursing experiences with an ethanol-intoxicated dam. Alcohol Clin Exp Res28:895–905, 2004.
83.
Pueta M, Abate P, Spear NE, Molina JC. Interactions between pre-and early postnatal alcohol-related memories: impact upon alcohol acceptance patterns. Int J Comp Psicol18:207–224, 2005.
84.
Pautassi RM, Sanders S, Miller S, Spear N, Molina JC. Early ethanol’s anxiolytic effects assessed through an unconditional stimulus revaluation procedure. Alcohol Clin Exp Res30:448–459, 2006.
85.
Molina JC, Bannoura MD, Chotro MG, McKinzie DL, Arnold HM, Spear NE. Alcohol-mediated tactile conditioned aversions in infant rats: devaluation of conditioning through alcohol-sucrose association. Neurobiol Learn Mem66:121–132, 1996.
86.
Hunt PS, Molina JC, Spear LP, Spear NE. Ethanol-mediated taste aversions and state-dependency in preweanling (16 day old) rats. Behav Neural Biol54:300–322, 1990.
87.
Hunt PS, Spear LP, Spear NE. An ontogenetic comparison of ethanol-mediated taste aversion learning and ethanol-induced hypothermia in preweanling rats. Behav Neurosci105:971–983, 1991.
88.
Pautassi RM, Godoy JC, Spear NE, Molina JC. Ethanol’s responsiveness to stimuli paired with different stages within the state of alcohol intoxication. Alcohol Clin Exp Res26:644–654, 2002.
89.
Cheslock SJ, Varlinskaya EI, Petrov ES, Silveri MM, Spear LP, Spear NE. Ethanol as a reinforcer in the newborn’s first suckling experience. Alcohol Clin Exp Res25:391–402, 2001.
90.
Petrov ES, Varlinskaya EI, Smotherman WP. Self-administration of ethanol and saccharin in newborn rats: effects on suckling plasticity. Behav Neurosci115:1318–1331, 2001.
91.
Petrov ES, Varlinskaya EI, Spear NE. Reinforcement from pharmacological effects of ethanol in newborn rats. Alcohol Clin Exp Res27: 1583–1591, 2003.
92.
Pautassi RM, Melloni C, Ponce LF, Molina JC. Acute ethanol counteracts the acquisition of aversive olfactory learning in infant rats. Alcohol36:99–105, 2005.
93.
Chotro MG, Molina JC. Acute ethanol contamination of the amniotic fluid during gestational day 21: postnatal changes in ethanol responsiveness in rats. Dev Psychobiol23:535–547, 1990.
94.
Chotro MG, Molina JC. Bradycardic responses elicited by alcohol odor in rat neonates: influence of in utero experience with alcohol. Psychopharmacology (Berl)106:491–496, 1992.
95.
Chotro MG, Cordoba NE, Molina JC. Acute prenatal experience with alcohol in the amniotic fluid: interactions with aversive and appetitive alcohol orosensory learning in the rat pup. Dev Psychobiol24:431–451, 1991.
96.
Ronca AE, Alberts JF. Perinatal stimulation and adaptation of the neonate. Acta Paediatr Suppl416:8–15, 1996.
97.
Wilson DA, Sullivan RM. Neurobiology of associative learning in the neonate: early olfactory learning. Behav Neural Biol61:1–18, 1994.
98.
Molina JC, Chotro MG. Association between chemosensory stimuli and cesarean delivery in rat fetuses: neonatal presentation of similar stimuli increases motor activity. Behav Neural Biol55:42–60, 1991.
99.
Domínguez HD, Chotro MG, Molina JC. Alcohol in the amniotic fluid prior to cesarean delivery: effects of subsequent exposure to alcohol odor upon alcohol responsiveness. Behav Neural Biol60:129–138, 1993.
100.
Domínguez HD, López MF, Molina JC. Interactions between perinatal and neonatal associative learning defined by contiguous olfactory tactile stimulation. Neurobiol Learn Mem71:272–288, 1999.
101.
Domínguez HD, López MF, Chotro MG, Molina JC. Perinatal responsiveness to alcohol’s chemosensory cues as a function of prenatal alcohol administration during gestational days 17–20 in the rat. Neurobiol Learn Mem65:103–112, 1996.
102.
Domínguez HD, López MF, Molina JC. Neonatal responsiveness to alcohol odor and infant alcohol intake as a function of alcohol experience during late gestation. Alcohol16:109–117, 1998.
Arias C, Chotro MG. Increased preference for ethanol in the infant rat after prenatal ethanol exposure, expressed on intake and taste reactivity tests. Alcohol Clin Exp Res29:337–346, 2005.
105.
Chotro MG, Arias C. Prenatal exposure to ethanol increases ethanol consumption: a conditioned response? Alcohol 30:19–28, 2003.
106.
Arias C, Chotro MG. Increased palatability of ethanol after prenatal ethanol exposure is mediated by the opioid system. Pharmacol Biochem Behav83:434–442, 2005.
107.
Acquas E, Meloni M, Di Chiara G. Blockade of delta-opioid receptors in the nucleus accumbens prevents ethanol-induced stimulation of dopamine release. Eur J Pharmacol230:239–241, 1993.
108.
Critcher EC, Lin CI, Patel J, Myers RD. Attenuation of alcohol drinking in tetrahydroisoquinoline-treated rats by morphine and naltrexone. Pharmacol Biochem Behav18:225–229, 1983.
109.
Roberts AJ, McDonald JS, Heyser CJ, Kieffer BL, Matthes HWD, Koob GF, Gold LH. mu-Opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther293:1002–1008, 2000.
110.
Stromberg MF, Casale M, Volpicelli L, Volpicelli JR, O’Brien CP. A comparison of the effects of the opioid antagonists’ naltrexone, naltrindole and β-funaltrexamine on ethanol consumption in the rat. Alcohol15:281–289, 1998.
111.
Hill KG, Kiefer SW. Naltrexone treatment increases the aversiveness of alcohol in outbreed rat. Alcohol Clin Exp Res19:279–284, 1997.
112.
Roth TL, Sullivan RM. Consolidation and expression of a shock-induced odor preference in rat pups is facilitated by opioids. Physiol Behav78:135–142, 2003.
113.
Varlinskaya EI, Petrov ES, Smotherman WP. Classical conditioning in the fetal rat: reinforcing properties of dynorphin A (1–13). Behav Neurosci110:154–167, 1996.
114.
Spear NE, Molina JC. Animal studies may reveal the consequences of early exposure to alcohol for later patterns of use and abuse in humans. In: Carroll ME, Overmier JB, Eds. Animal Research for Human Health: Advancing Human Welfare Through Behavioral Science. Washington, DC: American Psychological Association, pp85–99, 2001.
115.
Nizhnikov ME, Molina JC, Varlinskaya EI, Spear NE. Prenatal ethanol increases postnatal ethanol reinforcement. Alcohol Clin Exp Res30:34–45, 2006.
Spear NE, Rudy J. Tests of learning and memory in the developing rat. In: Shair HN, Barr GA, Hofer MA, Eds. Developmental Psychobiology: Current Methodological and Conceptual Issues. New York: Oxford University Press, pp84–113, 1991.
120.
Miller JS, Molina JC, Spear NE. Ontogenetic differences in the expression of odor aversion learning in 4 and 8 day old rats. Dev Psychobiol23:319–330, 1990.
121.
Rudy J, Cheatle M. Ontogeny of associative learning: acquisition of odor aversions by neonatal rats. In: Spear NE, Campbell B, Eds. Ontogeny of Learning and Memory. New Jersey: Lawrence Erlbaum Associates, pp157–188, 1979.
122.
Petrov ES, Varlisnkaya EI, Smotherman WP. The newborn rat ingests fluids through a surrogate nipple: a new technique for the study of early suckling behavior. Physiol Behav62:693–696, 1997.
123.
Smotherman WP, Goffman D, Petrov ES, Varlinkaya EI. Oral grasping of a surrogate nipple by the newborn rat. Dev Psychobiol31: 3–17, 1997.
124.
Varlinskaya EI, Petrov ES, Cheslock SJ, Spear NE. A new model of ethanol self-administration in newborn rats: gender effects on ethanol ingestion through a surrogate nipple. Alcohol Clin Exp Res23:1368–1376, 1999.
125.
Abate P, Varlinskaya EI, Cheslock SJ, Spear NE, Molina JC. Neonatal activation of alcohol-related prenatal memories: impact upon the first suckling response. Alcohol Clin Exp Res26:1512–1522, 2002.
126.
Deweer B, Sara SJ, Hars B. Contextual cues and memory retrieval in rats: alleviation of forgetting by a pretest exposure to background stimuli. Animal Learn Behav8:255–272, 1980.
127.
Miller JS, Jagielo JA, Spear NE. Differential effectiveness of various prior-cuing treatments in the reactivation and maintenance of memory. J Exp Psychol Anim Behav Process17:249–258, 1991.
128.
Miller RR, Kasprow WJ, Schachtman TR. Retrieval variability sources and consequences. Am J Psychol99:145–218, 1986.
129.
Rescorla RA, Heth DC. Reinstatment of fear to an extinguished conditioned stimulus. J Exp Psychol Anim Behav Process1:88–95, 1975.
Rodríguez WA, Horne CA, Padilla JL. Effects of glucose and fructose on recently reactivated and recently acquired memories. Prog Neuropsychopharmacol Biol Psychiatry23:1285–1317, 1999.
132.
Spear NE. Retrieval of memories in animals. Psychol Rev80:163–194, 1973.
133.
Spear NE. The Processing of Memories: Forgetting and Retention. Hillsdale, NJ: Lawrence Erlbaum Associates, 1978.
134.
Myers RD. Alcohol’s effect on body temperature: hypothermia, hyperthermia, or poikilothermia? Brain Res Bull 7:209–220, 1981.
135.
Cunningham CL, Hawks DM, Niehus JS. Role of hypothermia in ethanol-induced conditioned taste aversion. Psychopharmacology95: 318–322, 1988.
136.
Johanson IB. Thermotaxis in neonatal rat pups. Physiol Behav23: 871–884, 1979.
137.
Ogilvie DM, Stinson RH. The effect of age on temperature selection by laboratory mice (Mus musculus). Can J Zool44:511–517, 1966.
138.
Hoffman CM, Flory GS, Alberts JR. Neonatal thermotaxis improves reversal of a thermally reinforced operant response. Dev Psychobiol34:87–99, 1999.
139.
Kraemer PJ, Hoffman H, Randall CK, Spear NE. Devaluation of Pavlovian conditioning in the 10-day-old rat. Anim Learn Behav20: 219–222, 1992.
140.
Abate P, Pepino MY, Spear NE, Molina JC. Fetal associative learning with ethanol: correlations between maternal hypothermia and neonatal responsiveness to chemosensory cues of the drug. Alcohol Clin Exp Res28:805–815, 2004.
141.
Abate P, Spear NE, Molina JC. Fetal and infantile alcohol-mediated associative learning in the rat. Alcohol Clin Exp Res25:989–998, 2001.
142.
Abate P, Haymal BO, Spear NE, Molina JC. Alcohol-mediated associative learning in utero: neonatal reactivation through re-exposure to the pharmacological effects of the drug. (Abstract) Alcohol Clin Exp Res 26(Suppl May):151A, 2002.
143.
Fernandez-Vidal JM, Molina JC. Socially mediated alcohol preferences in adolescent rats following interactions with an intoxicated peer. Pharmacol Biochem Behav79:229–341, 2004.
144.
Hunt PS, Lant GM, Carroll CA. Enhanced intake of ethanol in preweanling rats following interactions with intoxicated siblings. Dev Psychobiol37:90–99, 2000.
145.
Hunt PS, Holloway JL, Scordalakes EM. Social interactions with an intoxicated sibling can result in increased intake of ethanol by periadolescent rats. Dev Psychobiol38:101–109, 2001.
146.
Mennella JA, Garcia PL. Children’s hedonic response to the smell of alcohol: effects of parental drinking habits. Alcohol Clin Exp Res8: 1167–1171, 2000.
147.
Noll RB, Zucker RA, Greenberg GS. Identification of alcohol by smell among preschoolers: evidence for early socialization about drugs occurring in the home. Child Dev61:1520–1527, 1990.
148.
Chotro MG, Spear NE. Repeated exposure to moderate doses of alcohol in the rat fetus: evidence of sensitization to toxic and chemosensory aspects of alcohol. Alcohol Clin Exp Res21:360–367, 1997.
149.
Gruest N, Richer P, Hars B. Emergence of long-term memory for conditioned aversion in the rat fetus. Dev Psychobiol44:189–198, 2004.
150.
Niznikov ME, Varlinskaya EI, Spear NE. Reinforcing effects of central ethanol injections in newborn rat pups. Alcohol Clin Exp Res30: 2089–2098, 2006.
151.
Froehlich JC. Interactions between alcohol and the endogenous opioid system. In: Zakhari S, Ed. Alcohol and the Endocrine System. Bethesda, MD: U.S. Department of Health and Human Services, National Institute on Alcohol Abuse and Alcoholism Research Monograph No. 23, pp31–35.
152.
Herz A. Endogenous opioid systems and alcohol addiction. Psychopharmacology (Berl)129:99–111, 1997.
153.
Koob GF. Neural mechanisms of drug reinforcement. Ann N Y Acad Sci654:171–191, 1992.
McBride WJ, Li TK. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol12: 339–369, 1998.
156.
Nizhnikov ME, Varlinskaya EI, Petrov ES, Spear NE. Reinforcing properties of ethanol in neonatal rats: involvement of the opioid system. Behav Neurosci120:267–28, 2006.
157.
Hudson R. Olfactory imprinting. Curr Opin Neurobiol3:548–52, 1993.
Schneider ML, Moore CF, Barnhart TE, Larson JA, DeJesus OT, Mukheriee J, Nickles RJ, Converse AK, Roberts AD, Kraemer GW. Moderate-level prenatal alcohol exposure alters striatal dopamine system function in rhesus monkeys. Alcohol Clin Exp Res29:1685–1697, 2005.
160.
Ebrahim SH, Luman ET, Floyd RL, Murphy CC, Bennett EM, Boyle CA. Alcohol consumption by pregnant women in the United States during 1988–1995. Obstet Gynecol92:187–192, 1998.
161.
Savage DD, Becher M, de la Torre AJ, Sutherland RJ. Dose-dependent effects of prenatal ethanol exposure on synaptic plasticity and learning in mature offspring. Alcohol Clin Exp Res26:1752–1758, 2002.
162.
Mameli M, Valenzuela CF. Alcohol increases efficacy of immature synapses in a neurosteroid-dependent manner. Eur J Neurosci23:835–839, 2006.
163.
Rice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect108(Suppl 3):511–533, 2000.
164.
Young C, Olney JW. Neuroapoptosis in the infant mouse brain triggered by a transient small increase in blood alcohol concentration. Neurobiol Dis22:548–554, 2006.
165.
Arias C, Mlewski C, Pautassi R, Spear NE, Molina JC. Infantile behavioral sensitivity to ethanol as a function of late prenatal exposure to the drug (abstract). Alcohol Clin Exp Res31:182A, 2007.
166.
Hudson, R. Olfactory imprinting. Curr Opin Neurobiol3:548–552, 1993.
167.
Leon M. Neuroethology of olfactory preference. J Neurobiol23: 1557–1573, 1992.
168.
McLean JH, Harley CW. Olfactory learning in the rat pup: a model that may permit visualization of a mammalian memory trace. Neuroreport15:1691–1697, 2004.
169.
Chotro MG, Kraebel KS, McKinzie DL, Molina JC, Spear NE. Prenatal and postnatal ethanol exposure influences preweanling rat’s behavioral and autonomic responding to ethanol odor. Alcohol13: 377–385, 1996.
170.
Pepino MY, López MF, Spear NE, Molina JC. Infant rats respond differentially to alcohol after nursing from an alcohol intoxicated dam. Alcohol18:189–201, 1999.
171.
Fernández-Vidal JM, Melloni C, Spear NE, Molina JC. Interactions between prenatal alcohol exposure and socially transmitted alcohol preferences in juvenile rats. Alcohol Clin Exp Res 27(Suppl June): 130A, 2003.
172.
Malanga CJ, Kosofsky BE. Does drug abuse beget drug abuse? Behavioral analysis of addiction liability in animal models of prenatal drug exposure. Dev Brain Res147:47–57, 2003.
173.
Alati R, Al Mamum A, Williams GM, O’Callagan M, Njman JA, Bor W. In utero alcohol exposure and prediction of alcohol disorders in early adulthood. Arch Gen Psychiatry63:1009–1016, 2006.
174.
Baer JS, Sampson PD, Barr HM, Conner PD, Streissguth AP. Prenatal alcohol exposure and family history of alcoholism in the etiology of adolescent alcohol problems. J Stud Alcohol59:533–543, 1998.
175.
Baer JS, Sampson PD, Barr HM, Connor PD, Streissguth AP. A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking. Arch Gen Psychiatry60:377–386, 2003.
176.
Griesler PC, Kandel DB. The impact of maternal drinking during and after pregnancy on the drinking of adolescent offspring. J Stud Alcohol59:292–304, 1998.
177.
Yates WR, Cadoret RJ, Troughton EP, Stewart M, Giunta TS. Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol and drug dependence. Alcohol Clin Exp Res22:914–920, 1998.
178.
Roberts AD, Moore CF, DeJesus OT, Barnhart TE, Larson JA, Mukherjee J, Nickles RJ, Schueller MJ, Shelton SE, Schneider ML. Prenatal stress, moderate fetal alcohol, and dopamine system function in rhesus monkeys. Neurotoxicol Teratol26:169–178, 2004.
179.
Schen RY, Hannigan, JH, Kapatos G. Prenatal ethanol reduces the activity of adult midbrain dopamine neurons. Alcohol Clin Exp Res23:1801–1807, 1999.
180.
Costa ET, Savage DD, Valenzuela CF. A review of the effects of prenatal or early postnatal ethanol exposure on brain lingand-gated ion channels. Alcohol Clin Exp Res24:706–715, 2000.
181.
Olney JW. Fetal alcohol syndrome at the cellular level. Addiction Biol9:137–149, 2004.
182.
Johnson JL, Leff M. Children of substance abusers: overview of research findings. Pediatrics103:1085–1099, 1999.
183.
Streissguth A, Barr H, Kogan J, Bookstein F. Primary and secondary disabilities in fetal alcohol syndrome. In: Streissguth A, Kanter J, Eds. The Challenge of Fetal Alcohol Syndrome. Overcoming Secondary Disabilities. Seattle, WA: University of Washington Press, pp25–39, 1997.
184.
Wong MM, Brower KJ, Fitzgeral HE, Zucker RA. Sleep problems in early childhood and early onset of alcohol and other drug use in adolescence. Alcohol Clin Exp Res28:578–587, 2004.
185.
Day NL, Richardson GA. An analysis of the effects of prenatal alcohol exposure on growth: a teratological model. Am J Med Genet C Semin Med Genet127:28–34, 2004.
186.
Mulder EJ, Morssink LP, van der Schee T, Visser GH. Acute maternal alcohol consumption disrupts behavioral state organization in the near-term fetus. Pediatr Res44:774–779, 1998.
187.
National Association of State Alcohol and Drug Abuse Directors, Inc. Alcohol Research on Prenatal Alcohol Exposure, Prevention, and Implication for State AOD Systems. State Issue Brief No. 2 prepared for the National Institute on Alcohol Abuse and Alcoholism, August 2005.
