Stimulation-evoked dopamine release in the nucleus accumbens following cocaine administration in rats perinatally exposed to polychlorinated biphenyls.
Exposure to polychlorinated biphenyls (PCBs) alters brain dopamine (DA) concentrations and DA receptor/transporter function, suggesting the reinforcing properties of drugs of abuse acting on the DA system may be affected by PCB exposure. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day PCBs from 4 weeks prior to breeding until litters were weaned on postnatal day 21. In vivo fixed potential amperometry (FPA) was used in adult anesthetized offspring to determine whether perinatal PCB exposure altered (1) presynaptic DA autoreceptor (DAR) sensitivity, (2) electrically evoked nucleus accumbens (NAc) DA efflux following administration of cocaine, and (3) the rate of depletion of presynaptic DA stores. One adult male and female littermate were tested using FPA following a single injection of cocaine (20 mg/kg ip), whereas a second adult male and female littermate were tested following the last of seven daily cocaine injections of the same dose. The carbon fiber recording microelectrode was positioned in the NAc core, and DA oxidation currents (i.e., DA release) evoked by brief stimulation of the medial forebrain bundle (MFB) were quantified before and after administration of cocaine. PCB-exposed rats exhibited enhanced stimulation-evoked DA release (relative to baseline) following a single injection of cocaine. Although nonexposed controls exhibited typical DA sensitization following repeated cocaine administration, this effect was attenuated in PCB-exposed rats. In addition, DAR sensitivity was higher (males only), and the rate of depletion of presynaptic DA stores was greater in PCB-exposed animals relative to nonexposed controls. These results indicate that perinatal PCB exposure can modify DA synaptic transmission in the NAc in a manner previously shown to alter the reinforcing properties of cocaine.
['Fielding|Jenna R|JR|', 'Rogers|Tiffany D|TD|', 'Meyer|Abby E|AE|', 'Miller|Mellessa M|MM|', 'Nelms|Jenna L|JL|', 'Mittleman|Guy|G|', 'Blaha|Charles D|CD|', 'Sable|Helen J K|HJ|']
D000818:Animals D000831:Animals, Newborn D017660:Autoreceptors D000697:Central Nervous System Stimulants D003042:Cocaine D004298:Dopamine D004305:Dose-Response Relationship, Drug D004558:Electric Stimulation D005260:Female D008297:Male D018811:Maternal Exposure D009714:Nucleus Accumbens D011078:Polychlorinated Biphenyls D011247:Pregnancy D011297:Prenatal Exposure Delayed Effects D017729:Presynaptic Terminals D051381:Rats D020318:Rats, Long-Evans D011954:Receptors, Dopamine D009435:Synaptic Transmission D013997:Time Factors D014886:Weaning
behavioral sensitization. neurotoxicology