Prenatal stress enhances responsiveness to cocaine.

TitlePrenatal stress enhances responsiveness to cocaine.
Publication TypeJournal Article
Year of Publication2008
AuthorsKippin TE, Szumlinski KK, Kapasova Z, Rezner B, See RE
Date Published2008 Mar
KeywordsAnimals, Animals, Newborn, Behavior, Addictive, Behavior, Animal, Brain Chemistry, Chromatography, High Pressure Liquid, Cocaine, Conditioning, Operant, Dopamine Uptake Inhibitors, Exploratory Behavior, Female, Male, Microdialysis, Motor Activity, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Rats, Sprague-Dawley, Reinforcement (Psychology), Self Administration, Stress, Psychological

Early environmental events have profound influences on a wide range of adult behavior. In the current study, we assessed the influence of maternal stress during gestation on psychostimulant and neurochemical responsiveness to cocaine, cocaine self-administration, and reinstatement of cocaine-seeking in adult offspring. Pregnant, female Sprague-Dawley rats were subjected to either no treatment or to restraint stress three times per day for the last 7 days of gestation and cocaine-related behavior was assessed in offspring at 10 weeks of age. Relative to controls, a noncontingent cocaine injection elevated locomotor activity as well as nucleus accumbens levels of extracellular dopamine and glutamate to a greater extent in both cocaine-naive and cocaine-experienced prenatal stress (PNS) rats and elevated prefrontal cortex dopamine in cocaine-experienced PNS rats. To assess the impact of PNS on cocaine addiction-related behavior, rats were trained to lever press for intravenous (i.v.) infusions of cocaine (0.25, 0.5, or 1 mg/kg/infusion), with each infusion paired with a light+tone-conditioned stimulus. Lever-pressing was extinguished and cocaine-seeking reinstated by re-exposure to the conditioned cues or by intraperitoneal cocaine-priming injections (5 or 10 mg/kg). PNS elevated active lever responding both during extinction and cocaine-primed reinstatement, but not during self-administration or conditioned-cued reinstatement. PNS also did not alter intake during self-administration. These findings demonstrate that PNS produces enduring nervous system alterations that increase the psychomotor stimulant, motivational, and neurochemical responsiveness to noncontingent cocaine. Thus, early environmental factors contribute to an individual's initial responsiveness to cocaine and propensity to relapse to cocaine-seeking.

Alternate JournalNeuropsychopharmacology
PubMed ID17487224
PubMed Central IDPMC2747653
Grant ListC06 RR015455 / RR / NCRR NIH HHS / United States
DA015369 / DA / NIDA NIH HHS / United States
DA016511 / DA / NIDA NIH HHS / United States
DA021161 / DA / NIDA NIH HHS / United States
P50 DA016511 / DA / NIDA NIH HHS / United States
P50 DA016511-010001 / DA / NIDA NIH HHS / United States