ROLE OF ESTRADIOL IN ANIMALS PRENATALLY EXPOSED TO AMPHETAMINE ON STRESS RESPONSE AND DOPAMINE RECEPTORS IN THE NUCLEUS ACCUMBENS

PENNACHIO GISELA; NEIRA FLAVIA; PIETROBON E; VALDEZ SUSANA; BREGONZIO CLAUDIA; SOAJE MARTA

mar del plata

Congreso; LXI reunion anual de la sociedad argentina de investigacion clinica; 2016

saic

The psychostimulants activate the same neurobiological substratesthan stress response. Prenatal exposure to amphetamine(PEA) induces endurable changes that become manifest in theadulthood. These changes can be expressed as an altered centraldopaminergic activity. Sex steroids modulate brain dopaminergicsystems and may influence the neuroadaptive changes induced byamphetamine. Stress exposure induces dopamine release in themesolimbic pathway and the activation of hypothalamic-pituitaryadrenalaxis. Our aim was to evaluate the effect of estradiol in PEAanimals in response to stress and dopaminergic receptors and tyrosinehydroxylase (TH) expression in nucleus accumbens. To thispurpose, female rats were treated daily with amphetamine 2,5mg/kg i.p or saline during days 15 to 21 of pregnancy. Their offspringwere ovariectomized (OVX) at day 60, treated with estrogen (E2) (2x 5ug/rat/24 h) or oil 15 days later, and subjected to immobilizationstress during 2 h. Blood and tissue samples were collected to determinecorticosterone by RIA and dopamine receptors (D1R, D2R,D3R) and TH expression by real time PCR in extracts of nucleusaccumbens. Stress exposure increased corticosterone levels inOVX (basal: 109,19 ±44,57 ng/ml vs stress: 214,41±21,49 ng/ml)and OVX+E2 (basal: 157,24±33,87 ng/ml vs stress: 364,04±23,75ng/ml), in both groups PEA blunted the corticosterone response tostress. PEA induced a decrease in basal D3R expression and anincrease in TH expression in response to stress, both responseswere E2 dependent. No change was observed in D1R and D2Rexpression. We conclude that the neuroadaptive response inducedby PEA in nucleus accumbens is under estrogen influence. Moreover,an altered stress response should be considered betweenthe neuroadaptive changes induced by PEA.