Early Adoption Modifies the Effects of Prenatal Stress on Dopamine and Glutamate Receptors in Adult Rat Brain Virginia G. Barros, 1 Marı ´a A. Berger, 1 Irene D. Martijena, 2 Marı ´a I. Sarchi, 3 Adriana A. Pe ´rez, 4 Victor A. Molina, 2 Frank I. Tarazi, 5,6 and Marta C. Antonelli 1 * 1 Instituto de Quı ´mica y Fisicoquı ´mica Biolo ´gicas (UBA-CONICET), Facultad de Farmacia y Bioquı ´mica, Universidad de Buenos Aires, Buenos Aires, Argentina 2 Departmento de Farmacologı ´a, Facultad de Ciencias Quı ´micas, Universidad de Co ´rdoba, Co ´ rdoba, Argentina 3 Departamento de Fisicomatema ´tica, Facultad de Farmacia y Bioquı ´mica, Universidad de Buenos Aires, Buenos Aires, Argentina 4 Laboratorio de Biometrı ´a, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina 5 Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, Massachusetts 6 Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, Massachusetts Stressful stimuli during pregnancy induce complex effects that influence the development of offspring. These effects can be prevented by environmental manipulations during the early postnatal period. Repeated restraint during the last week of pregnancy was used as a model of prenatal stress, and adoption at birth was used to change the post- natal environment. No differences were found in various physical landmarks, except for testis descent, for which all prenatally stressed pups showed a 1-day delay in compar- ison with control rats, regardless of the postnatal adoption procedure. Levels of dopamine (DA) D 2 and glutamate (Glu) N-methyl-D-aspartate (NMDA) receptors were differentially regulated in different forebrain regions of cross-fostered adult offspring. Increased concentrations of cortical D 2 re- ceptors detected in stressed pups, raised by a gestationally stressed biological mother, were not detected when the pups were raised by a control mother. Control pups raised by a foster mother whether gestationally stressed or not had higher levels of NMDA receptors in cortical areas. These findings suggest that the normal expression of DA and Glu receptors is influenced by in utero experience and by lactation. The complex pattern of receptor changes re- flects the high vulnerability of DA and Glu systems to vari- ations both in prenatal and in postnatal environment, par- ticularly for cortical D 2 receptors and NMDA receptors in cerebral cortex and nucleus accumbens. In contrast, testis descent appears to be more susceptible to prenatal than to postnatal environmental events. © 2004 Wiley-Liss, Inc. Key words: dopamine D 2 receptors; glutamate NMDA receptors; testis descent; prenatal stress; cross-foster- ing; quantitative autoradiography Offspring of pregnant female animals exposed to stress prenatally have higher vulnerability to anxiety, ab- normal circadian rhythm, impaired sexual function, and enhanced propensity to self-administer drugs of abuse (Henry et al., 1995; Valle ´e et al., 1999). Such vulnerability may result from abnormalities in the development and integration of forebrain dopamine (DA) and glutamate (Glu) projections during the prenatal period. In this re- gard, prenatal stress altered DA neurotransmission, evi- denced by a higher DA turnover in prefrontal cortex and a lower turnover in striatum and nucleus accumbens (Fride and Weinstock, 1988; Alonso et al., 1997). In addition, DA D 2 and D 3 receptors were increased and decreased, respectively, in nucleus accumbens of mature adults sub- jected to restraint prenatal stress (Henry et al., 1995). We have recently assessed the effects of prenatal stress on DA and Glu receptor expression in adult rats subjected to repeated restraint stress during the last week of pregnancy and found that these animals have higher levels of DA D 2 and Glu metabotropic group III receptors in cortical re- gions and higher concentrations of N-methyl-D-aspartate (NMDA) receptors in cerebral cortex and basal ganglia compared with their control littermates (Berger et al., 2002). Several behavioral strategies have been employed to modify the postnatal environment, namely, postnatal han- dling, early adoption (or cross-fostering), and maternal Contract grant sponsor: Agencia Nacional de Promocio ´n Cientı ´fica y Tecnolo ´ gica; Contract grant number: PICT 02287; Contract grant sponsor: CONICET; Contract grant number: PIP 6266. *Correspondence to: Marta C. Antonelli, IQUIFIB, Facultad de Farmacia y Bioquı ´mica, Junı ´n 956, 1113 Buenos Aires, Argentina. E-mail: mca@mail.retina.ar Received 2 December 2003; Revised 5 February 2004; Accepted 17 February 2004 Published online 9 April 2004 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/jnr.20119 Journal of Neuroscience Research 76:488 – 496 (2004) © 2004 Wiley-Liss, Inc.