PMID- 15380828
OWN - NLM
STAT- MEDLINE
DCOM- 20041202
LR  - 20200106
IS  - 0736-5748 (Print)
IS  - 0736-5748 (Linking)
VI  - 22
IP  - 5-6
DP  - 2004 Aug-Oct
TI  - Prenatal intravenous cocaine and the heart rate-orienting response: a 
      dose-response study.
PG  - 285-96
AB  - Attentional dysfunction is a persistent behavioral abnormality that is emerging 
      as one of the cardinal features in the investigations of the teratogenic effects 
      of cocaine in humans and rodents. The present study sought to extend this work by 
      using a dose-response design with an alternate strain of rat. Virgin Long-Evans 
      female rats, implanted with an IV access port prior to breeding were administered 
      saline, 0.5, 1.0, or 3.0 mg/kg of cocaine HCl from gestational day (GD) GD8-21 
      (1x per day-GD8-14, 2x per day-GD15-21). Cocaine had no significant effect on 
      maternal or litter parameters. At 14-15 days of age, 1 male and 1 female from 
      each litter were tested to evaluate the heart rate orienting response (HR-OR). 
      Following 20 min for acclimation, pups were presented an olfactory stimulus for 
      20s per trial, across four trials, and with an intertrial interval of 2 min. The 
      initial baseline HR was not significantly different across the treatment groups, 
      although cocaine did alter the stability of the QRS complex duration. The 
      magnitude of the HR-OR averaged across trials increased as a linear function of 
      dosage of cocaine. A more complex (quadratic) interaction between cocaine dose 
      and sex of the offspring was also noted. When examined across trials, the 
      controls failed to display any significant within-session variation in the HR-OR; 
      in contrast all of the prenatal cocaine treated groups displayed either 
      sensitization (low and high dose) or habituation of the response (middle dose). 
      Analysis of the peak HR-OR confirmed that the controls were indeed displaying the 
      response on at least one trial of the session, albeit not consistently on any 
      specific trial. The more vigorous HR-OR of the prenatal cocaine groups, relative 
      to vehicle controls, most likely reflects an alteration in development of the 
      neural basis of response; as previously shown, the most vigorous response to the 
      olfactory stimulus is seen early (12 days of age) and progressively decreases 
      across the preweaning period. In sum, prenatal exposure to cocaine, at least when 
      administered by the IV route, provides reproducible alterations in attentional 
      processes, as indexed by the noradrenergically-mediated HR-OR. The documentation 
      of a linear dose-response function suggests that there is likely no threshold for 
      the drug-induced alteration. Moreover, the sex of the animal also appears to play 
      some role in the nature of the expression of the altered HR-OR.
FAU - Foltz, Tara L
AU  - Foltz TL
AD  - Department of Biology, University of Kentucky, Lexington, KY, USA.
FAU - Snow, Diane M
AU  - Snow DM
FAU - Strupp, Barbara J
AU  - Strupp BJ
FAU - Booze, Rosemarie M
AU  - Booze RM
FAU - Mactutus, Charles F
AU  - Mactutus CF
LA  - eng
GR  - DA13137/DA/NIDA NIH HHS/United States
GR  - DA12719/DA/NIDA NIH HHS/United States
GR  - R01 DA012719/DA/NIDA NIH HHS/United States
GR  - DA13965/DA/NIDA NIH HHS/United States
GR  - DA09160/DA/NIDA NIH HHS/United States
GR  - R01 DA013137/DA/NIDA NIH HHS/United States
GR  - HD043680/HD/NICHD NIH HHS/United States
GR  - DA14401/DA/NIDA NIH HHS/United States
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arousal/*drug effects
MH  - Attention/*drug effects
MH  - Cocaine/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Gestational Age
MH  - Habituation, Psychophysiologic/*drug effects
MH  - Heart Rate/*drug effects/*physiology
MH  - Injections, Intravenous
MH  - Male
MH  - Maternal-Fetal Exchange/physiology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Long-Evans
MH  - Retention, Psychology/drug effects
EDAT- 2004/09/24 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/09/24 05:00
PHST- 2004/03/15 00:00 [received]
PHST- 2004/05/27 00:00 [revised]
PHST- 2004/05/27 00:00 [accepted]
PHST- 2004/09/24 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/09/24 05:00 [entrez]
AID - S0736574804000656 [pii]
AID - 10.1016/j.ijdevneu.2004.05.010 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):285-96. doi: 
      10.1016/j.ijdevneu.2004.05.010.