PMID- 19520673
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20211020
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 111
IP  - 1
DP  - 2009 Sep
TI  - Vulnerability to (+)-methamphetamine effects and the relationship to drug 
      disposition in pregnant rats during chronic infusion.
PG  - 27-36
LID - 10.1093/toxsci/kfp127 [doi]
AB  - Chronic (+)-methamphetamine (METH) use during pregnancy increases the health risk 
      for both mother and fetus. To provide insights into these risks, the relationship 
      between changes in METH disposition and METH-induced pharmacological effects were 
      studied in Sprague-Dawley rat dams and litters. Timed-pregnant rats (n = 5-6) 
      were given saline or METH (5.6-17.8 mg/kg/day) by continuous sc infusion from 
      gestational day (GD) 7 (before organogenesis) until GD21 (0-2 days before 
      delivery). By GD11, all rats in the 17.8-mg/kg/day group died or were sacrificed 
      for humane reasons. There were significant (p < 0.05) dose- and gestational 
      time-dependent decreases in maternal body weight in the 10- to 13.2-mg/kg/day 
      groups, which slowly recovered to near normal by GD21. Continued METH dosing in 
      the surviving groups did not affect the mean pups/litter weight at the end of the 
      experiment on GD21. While maternal and fetal METH and (+)-amphetamine serum 
      concentrations were similar on GD21, brain concentrations were significantly 
      greater in the dams (p < 0.05). Importantly, brain-to-serum ratios in the dams 
      were 9:1 and 3:1 in the pups. METH systemic clearance (Cl(S)) in dams 
      significantly (p < 0.05) decreased from 52 +/- 14 ml/min/kg on GD10 to 28 +/- 6 
      ml/min/kg on GD21 in all dose groups, indicating late-gestational stage 
      reductions in METH Cl(S). Overall, these findings suggest that there were two 
      periods of increased susceptibility for dams and fetuses during chronic METH 
      treatment. First was the period after the start of METH dosing in which 
      neuroadaptation and tolerance to METH occurs in the adult. The second was at the 
      end of pregnancy when METH clearance was significantly reduced.
FAU - White, Sarah J
AU  - White SJ
AD  - Department of Pharmacology and Toxicology, College of Medicine, University of 
      Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
FAU - Laurenzana, Elizabeth M
AU  - Laurenzana EM
FAU - Gentry, William Brooks
AU  - Gentry WB
FAU - Hendrickson, Howard P
AU  - Hendrickson HP
FAU - Williams, David Keith
AU  - Williams DK
FAU - Ward, Keith W
AU  - Ward KW
FAU - Owens, Samuel Michael
AU  - Owens SM
LA  - eng
GR  - R01 DA007610-15/DA/NIDA NIH HHS/United States
GR  - T32EA07310/PHS HHS/United States
GR  - DA07610/DA/NIDA NIH HHS/United States
GR  - R01 DA007610-14/DA/NIDA NIH HHS/United States
GR  - R01 DA007610/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090610
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Blood Proteins)
RN  - 0 (Central Nervous System Stimulants)
RN  - 44RAL3456C (Methamphetamine)
RN  - TZ47U051FI (Dextroamphetamine)
SB  - IM
MH  - Animals
MH  - Blood Proteins/metabolism
MH  - Brain/metabolism
MH  - Central Nervous System Stimulants/administration & 
      dosage/*pharmacokinetics/*toxicity
MH  - Dextroamphetamine/administration & dosage/pharmacokinetics/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fetal Development/drug effects
MH  - Fetus/drug effects/metabolism
MH  - Gestational Age
MH  - Infusions, Intravenous
MH  - Methamphetamine/administration & dosage/*pharmacokinetics/*toxicity
MH  - Motor Activity/drug effects
MH  - Pregnancy
MH  - Protein Binding
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stereotyped Behavior/drug effects
PMC - PMC2726297
EDAT- 2009/06/13 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/09/01
CRDT- 2009/06/13 09:00
PHST- 2009/06/13 09:00 [entrez]
PHST- 2009/06/13 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - kfp127 [pii]
AID - 10.1093/toxsci/kfp127 [doi]
PST - ppublish
SO  - Toxicol Sci. 2009 Sep;111(1):27-36. doi: 10.1093/toxsci/kfp127. Epub 2009 Jun 10.