Perinatal flunitrazepam exposure causes persistent alteration of parvalbumin-immunoreactive interneuron localization in rat prefrontal cortex.
GABA regulates proliferation via GABAA receptors during development of the neocortex. We recently demonstrated that the endogenous GABAA receptor modulator allopregnanolone plays a role in regulating normal neurodevelopment in prefrontal cortex. Benzodiazepine exposure during early development produces marked behavioral changes in adult rats. To determine if exposure to benzodiazepines during development alters GABAergic interneurons in prefrontal cortex (PFC), rat pups were exposed to flunitrazepam (2.5 mg/kg) on postnatal day (P) 2 and assayed for parvalbumin- and calbindin-immunoreactivity on P80. The ratio of parvalbumin labeled cells in deep vs. superficial layers increased five-fold; calbindin-immunoreactivity and total cell number were not altered. These data are consistent with altered distribution of a subset of interneurons after benzodiazepine exposure and suggest a role for GABAA receptor modulation in normal development of GABAergic systems in PFC.
Grobin
A Chistina
AC
Department of Psychiatry, Pharmacology and Bowles Center for Alcohol Studies, CB #7160, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA. grobinac@med.unc.edu
Lieberman
Jeffrey A
JA
Morrow
A Leslie
AL
D000818:Animals; D000831:Animals, Newborn; D005445:Flunitrazepam / Q000494:pharmacology*; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D010320:Parvalbumins / Q000032:analysis* / Q000096:biosynthesis; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism
D010320:Parvalbumins; D011963:Receptors, GABA-A; D005445:Flunitrazepam