Prenatal cocaine alters dopamine and sigma receptor binding in nucleus accumbens and striatum in dams and adolescent offspring.
Maternal cocaine abuse is a societal problem with serious impact on both mother and child. Few studies exist that study the mother/offspring dyad of neurological effects of maternal cocaine abuse. The present study was designed to study alterations in D2, D3 and sigma receptor density in nucleus accumbens and striatum of dams and male and female offspring following gestational cocaine. Long-Evans female rats were implanted with an intravenous (i.v.) access port prior to breeding and were administered saline or 3.0 mg/kg of cocaine from gestational day (GD) GD8-20 (1 injection/day-GD8-14, 2 injections/day-GD15-20). Offspring were raised by maternal dams and allowed to mature until postnatal days 31-35, at which time dams and offspring were sacrificed for assay of radioligand binding. In dams, decreased D2 (24.6%) and D3 (36.9%) binding was observed in striatum. Female offspring displayed no differences in receptor binding in either region. Male offspring displayed decreased D2 receptor binding (27.1%) in nucleus accumbens and increased D3 (75.2% and 33.5%) and sigma receptor binding (73.4% and 53.1%) in accumbens and striatum, respectively. Collectively, these data clearly demonstrate that male offspring exhibit significant alterations in D2, D3 and sigma receptor binding. These results suggest that dams and offspring display long-lasting alterations (5 weeks) in dopamine receptor binding. These alterations in dopamine and sigma receptor binding in offspring following prenatal cocaine and rearing by maternal dams are sex specific and could have profound effects on the development of behavior.
Silvers
J M
JM
University of South Carolina, Department of Psychology, Physiology and Pharmacology, Program in Behavioral Neuroscience, Columbia, SC 29208, USA. silversj@gwm.sc.edu
Wallace
D R
DR
Harrod
S B
SB
Mactutus
C F
CF
Booze
R M
RM
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000493:pharmacokinetics; D003042:Cocaine / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006146:Guanidines / Q000493:pharmacokinetics*; D007554:Isotopes / Q000493:pharmacokinetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*; D012737:Sex Factors; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics
D001549:Benzamides; D006146:Guanidines; D007554:Isotopes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017480:Receptors, sigma; D013764:Tetrahydronaphthalenes; C063525:epidepride; D003042:Cocaine; C050232:1,3-ditolylguanidine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin