Chronic exposure to benzyl butyl phthalate (BBP) alters social interaction and fear conditioning in male adult rats: alterations in amygdalar MeCP2, ERK1/2 and ERα.
OBJECTIVE
Benzyl Butyl Phthalate (BBP) is an industrial plasticizer that has an unknown action in the central nervous system. Phthalates have recently been associated with behavioral actions that are linked to their endocrine disrupting properties. The purpose of this study was to investigate the behavioral and molecular effects of BBP treatment in male rats.


METHODS
Male rats were chronically exposed to BBP in the drinking water (5.0 ppm and 10.0 ppm) throughout adolescence and into the adult phase of life. Their behavior was then assessed in a learning and memory task (fear conditioning), open field exploration and a test of sociability.


RESULTS
BBP treated rats showed decreased freezing in fear conditioning, no changes in open field exploration, and increased aberrant social behavior. Rats were sacrificed at post natal day 140 and blood and brains were harvested and processed. We found increased hormonally active estrogen, 17-β estradiol, in the serum of BBP treated rats. BBP treatment also induced changes in amygdalar proteins related to synaptic plasticity including decreased MeCP2 levels that correlated with tests of sociability with no changes in stress related proteins such as nuclear factor kappa B (NFkB). We also found alterations in physiological responses as measured by body weight without changes in food consumption suggesting disruption of metabolism and body homeostasis.


CONCLUSIONS
We suggest that BBP administration disrupts normal learning and social behavior, and that these effects could be related to alterations of amygdala function.
Department of Psychology, Quinnipiac University, 275 Mount Carmel Avenue, Hamden, CT, USA. adrienne.betz@quinnipiac.edu.
Adrienne
A
Betz
Sahani
S
Jayatilaka
Jugal
J
Joshi
Sriram
S
Ramanan
Danielle
D
Debartolo
Harry
H
Pylypiw
Emerson
E
Franke
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005239:Fear / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D010795:Phthalic Acids / Q000008:administration & dosage*; D051381:Rats; D012919:Social Behavior
D047628:Estrogen Receptor alpha; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D010795:Phthalic Acids; C027561:butylbenzyl phthalate