Gestational treatment with cocaine and fluoxetine alters oxytocin receptor number and binding affinity in lactating rat dams.
Cocaine administered chronically throughout gestation has been correlated with deficits in maternal behavior, increased maternal aggressive behavior and decreased oxytocin levels in rats. In addition to its effects on oxytocin levels, cocaine is a potent serotonergic, dopaminergic and noradrenergic reuptake inhibitor. Alterations in the dopaminergic and serotonergic systems have been suggested as possibly having a role in cocaine-induced maternal aggression. This study was in part, an attempt to understand some of the mechanisms by which cocaine increases postpartum aggression, particularly as they relate to changes in the oxytocin system. Oxytocin receptor number and binding affinity in the medial preoptic area of the hypothalamus, ventral tegmental area, hippocampus and amygdala were determined for lactating rat dams on postpartum day 6 (PPD 6) that were gestationally treated with cocaine, fluoxetine, saline or an amfonelic acid/fluoxetine drug combination. Cocaine and fluoxetine treatment both resulted in a significant up-regulation of oxytocin receptor number and lower receptor affinity in the amygdala of lactating rat dams compared to saline controls and the amfonelic acid/fluoxetine combination treatment group. Cocaine treatment also resulted in a significant down-regulation of oxytocin receptors in the medial preoptic area and both cocaine and fluoxetine treated dams had the highest affinity for oxytocin receptors in this brain region. Results of the present study support previous data indicating that alterations in oxytocinergic and perhaps serotonergic system dynamics in the amygdala may play a role in cocaine-induced postpartum aggression.
Johns
Josephine M
JM
Department of Psychiatry, The University of North Carolina at Chapel Hill, 424 Taylor Hall, CB #7096, Chapel Hill, NC 27599-7096, USA. jjohns@med.unc.edu
Lubin
Deborah A
DA
Walker
Cheryl H
CH
Joyner
Paul
P
Middleton
Christopher
C
Hofler
Vivian
V
McMurray
Matthew
M
D000818:Animals; D000831:Animals, Newborn; D000971:Antineoplastic Combined Chemotherapy Protocols; D001288:Attention / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage*; D005865:Gestational Age; D007275:Injections, Intravenous; D007774:Lactation / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011485:Protein Binding; D051381:Rats; D020318:Rats, Long-Evans; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012737:Sex Factors; D014018:Tissue Distribution
D009287:Naphthyridines; D018045:Receptors, Oxytocin; D005473:Fluoxetine; D009268:Nalidixic Acid; D003042:Cocaine; C006486:amfonelic acid