PMID- 9380002
OWN - NLM
STAT- MEDLINE
DCOM- 19971110
LR  - 20190920
IS  - 0892-0362 (Print)
IS  - 0892-0362 (Linking)
VI  - 19
IP  - 5
DP  - 1997 Sep-Oct
TI  - Behavioral effects of low-dose gestational day 11-13 retinoic acid exposure.
PG  - 355-62
AB  - In a comparison article we report that maternal PO exposure to 2.5 mg/kg 
      all-trans retinoic acid (RA) daily for 3 consecutive days over gestational days 
      (GD) 11-13 produces a 10% reduction in weight of cerebellum at 4 weeks of age, 
      not accompanied by other malformations. Here we report the results of a 
      preliminary behavioral analysis of offspring exposed gestationally to RA as 
      above. Exposed dams were allowed to deliver normally, and litters were culled to 
      eight pups (4 +/- 1 of each sex) at birth. Both male and female offspring were 
      tested prior to weaning on GD 21. Thereafter females were killed on postnatal day 
      (PND) 28 for verification of RA effects on regional brain weight, and all 
      subsequent behavioral testing was conducted on males. Preweaning tests were 
      restricted to negative geotaxis (PND 8-9) and open field activity (PND 22). 
      Postweaning tests included open field activity (PND 43), auditory startle 
      response (three times, on PNDs 22, 43, and 84), 2-week activity in residential 
      running wheels (PNDs 62-76), complex maze performance for 5 consecutive days (PND 
      83-87), emergence latency (PND 106), and assessment of the behavioral response to 
      an amphetamine challenge (PND 107). Males were then killed on PND 108 for 
      verification of RA effects on regional brain weights. In this study, RA reduced 
      weight of cerebellum but not striatum. Cerebellar weight was 92% of control 
      values in PND 28 females, and this weight difference had diminished to 95% of 
      control weight by PND 108 in males. There were no treatment effects on negative 
      geotaxis, activity in a small open field, auditory startle amplitude, or latency 
      to enter an illuminated alley from a dark chamber. Maze learning occurred at 
      levels equal to or slightly better than controls. Running wheel activity was 
      enhanced by RA exposure, whereas activity in response to an amphetamine challenge 
      was reduced by such exposure. We conclude that RA doses low enough to produce 
      mild weight reductions in cerebellum, without attendant malformations, can alter 
      behavior. The precise nature of these alterations remains to be elucidated, but 
      the findings reported here suggest that effects may be more pronounced on 
      activity than on learning.
FAU - Holson, R R
AU  - Holson RR
AD  - Division of Reproductive and Developmental Toxicology, National Center for 
      Toxicological Research, Jefferson, AR 72079, USA.
FAU - Gazzara, R A
AU  - Gazzara RA
FAU - Ferguson, S A
AU  - Ferguson SA
FAU - Adams, J
AU  - Adams J
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn/physiology
MH  - Avoidance Learning/drug effects
MH  - Behavior, Animal/*drug effects
MH  - Brain/drug effects/growth & development
MH  - Female
MH  - Gestational Age
MH  - Male
MH  - Maze Learning/drug effects
MH  - Motor Activity/drug effects
MH  - Organ Size/drug effects
MH  - Postural Balance/drug effects
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Reflex, Startle/drug effects
MH  - Tretinoin/*toxicity
MH  - Vocalization, Animal/drug effects
MH  - Weight Gain/drug effects
EDAT- 1997/10/06 00:00
MHDA- 1997/10/06 00:01
CRDT- 1997/10/06 00:00
PHST- 1997/10/06 00:00 [pubmed]
PHST- 1997/10/06 00:01 [medline]
PHST- 1997/10/06 00:00 [entrez]
AID - S0892-0362(97)00041-X [pii]
AID - 10.1016/s0892-0362(97)00041-x [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 1997 Sep-Oct;19(5):355-62. doi: 
      10.1016/s0892-0362(97)00041-x.