Neurobehavior effects in four strains of mice offspring exposed prenatally to alprazolam.
OBJECTIVE
This study was performed to determine whether prenatal exposure to alprazolam affects offspring behavior in different strains of mice.


METHODS
Eight to 11 gravid mice of the C3H/He, C57BL/6, A/J, and DBA/2 strains were given either an anxiolytic dose of alprazolam (0.32 mg/kg) or a placebo by gavage on day 18 of an anticipated 19- to 21-day gestation. Neurobehavior tasks were conducted to assess anxiety, learning and memory, and social interaction. Data were analyzed by analysis of variance or a Fisher exact probability test.


RESULTS
Anxiety in alprazolam-exposed offspring was reduced in C3H/He (P <.05) and A/J (P <.05) newborn infants by separation vocalization but may be increased in the C3H/He adult strain on the plus maze task. Learning was slower among C57BL/6 mice exposed to alprazolam (P <.01), whereas memory was reduced in exposed A/J and DBA/2 offspring (P <.05). Alprazolam exposure was associated with more aggression among C3H/He and C57BL/6 male offspring (P <.01) and with less group activity by C57BL/6 offspring (P <.05).


CONCLUSIONS
Altered behaviors in several mouse strains after prenatal exposure to alprazolam suggests a vulnerability of GABA-benozdiazepine receptor formation in fetal brain development.
Rayburn
William F
WF
Departments of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, 2211 Lomas Boulevard NE (ACC 4), Albuquerque, NM 87131, USA. wrayburn@salud.unm.edu
Christensen
H Dix
HD
Gold
Karen M
KM
Gonzalez
Christina L
CL
D000374:Aggression / Q000187:drug effects; D000525:Alprazolam / Q000009:adverse effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001010:Anxiety, Separation / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D007398:Interpersonal Relations; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009420:Nervous System / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013045:Species Specificity; D014828:Vocalization, Animal / Q000187:drug effects
D014151:Anti-Anxiety Agents; D000525:Alprazolam