SUN-222 - Anxiety-Like Behavior Developed by Exposure to the Endocrine Disruptor DEHP in Male Rats.

The endocrine disruptor di-(2-ethylhexyl) phthalate (DEHP) with an antiandrogenic effect and used in plastic manufactures, disrupts reproductive system and induced neurobehavioral changes. The aim of this study was to assess the effects of DEHP on the anxiety-like behavior in adult male rats and the potential participation of GABAergic system and / or testosterone regulation. Male offspring rats from mothers exposed orally to DEHP (30 mg/kg BW/day) from day 1 of gestation until weaning, were evaluated at 70 days of age using the elevated plus maze (EPM) anxiety assessment test. Some animals received 90 minutes pretest GABA-A agonist muscimol (2 mg/kg ip) or GABA-B agonist baclofen (10 mg/kg ip), or testosterone every 48 hs during 14 days pretest (0.1mg ip). We evaluated the anxiety behavioral parameters: Total arm entries in both arms (TAE), Frequency of open arm entries (%FEO), Time spent in open arms (%TSO), Time spent in closed arms (%TSC), Freezing (time in which animal remains immobile), head-dipping (time during the animal extends its head beyond the EPM arms) and Stretch-attend posture time (animal stretches its body forward while keeping the hind limbs in place). DEHP group shown a reduction in the TAE (p < 0.01); reversed by GABA-B agonists (p < 0.01) and testosterone (p < 0.0003). %FEO was lower in DEHP animals (p < 0.018), reversed by GABA-A (p < 0.02) and B agonists (p < 0.0001) and testosterone (p < 0.005). The %TSO was lower in DEHP group (p < 0.015), reversed by GABA-A (p < 0.012) and B agonists (p < 0.0001), and testosterone (p < 0.0001). In control animals GABA agonist did not produced change, but testosterone prolongated %TSO (p < 0.0001). A longer %TSC was seen in DEHP group (p < 0.0001). This effect was reversed by GABA-A and B agonists and testosterone administration (p < 0.0001). Meanwhile control animals that received testosterone, and GABA-B agonists showed a shorter %TSC (p < 0.0001). Animals exposed to DEHP showed a marked increase in freezing time (p < 0.0001), effect reversed by GABA-A and B agonists and testosterone (p < 0.0001). On the other hand, control that received GABAergic agonists or testosterone also showed a shorter freezing time (p < 0.0001). DEHP exposure resulted in a reduced head-dipping time (p < 0.0001), effect reversed by all GABAergic agonists and testosterone (p < 0.0001). DEHP exposure induced a significantly (p < 0.0001) longer stretch-attend posture time, also reversed by GABAergic agonists (p < 0.0001) and testosterone (p < 0.0001). In conclusion, pre and perinatal DEHP exposure increased the anxiety-like behavior in adult male rats, evidenced by a reduction in open arm exploration (%FEO, %TSO, head-dipping), increased in %TSC together with an increase freezing time and stretch-attend posture. These behavioral alterations are consequence of neuroendocrine alterations, since it could reverse by GABAergic agonists and testosterone treatment.