Role of estradiol in animals prenatally exposed to amphetamine on stress response and dopamine receptors in the nucleus accumbens.

PENNACCHI GE; NEIRA F; PIETROBON EO; JAHN GA; VALDEZ SR ; BREGONZIO C; SOAJE M

Mar del Plata

Congreso; 61 Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

SAIC

The psychostimulants activate the same neurobiologicalsubstratesthan stress response. Prenatal exposure to amphetamine(PEA) induces endurable changes that become manifestin theadulthood. These changes can be expressed as analtered centraldopaminergic activity. Sex steroids modulate braindopaminergicsystems and may influence the neuroadaptive changesinduced byamphetamine. Stress exposure induces dopamine releasein themesolimbic pathway and the activation ofhypothalamic-pituitaryadrenalaxis. Our aim was to evaluate the effect of estradiolin PEAanimals in response to stress and dopaminergicreceptors and tyrosinehydroxylase (TH) expression in nucleus accumbens. Tothispurpose, female rats were treated daily withamphetamine 2,5mg/kg i.p or saline during days 15 to 21 of pregnancy.Their offspringwere ovariectomized (OVX) at day 60, treated withestrogen (E2) (2x 5ug/rat/24 h) or oil 15 days later, and subjected toimmobilizationstress during 2 h. Blood and tissue samples werecollected to determinecorticosterone by RIA and dopamine receptors (D1R, D2R,D3R) and TH expression by real time PCR in extracts ofnucleusaccumbens. Stress exposure increased corticosteronelevels inOVX (basal: 109,19 ±44,57 ng/ml vs stress: 214,41±21,49ng/ml)and OVX+E2 (basal: 157,24±33,87 ng/ml vs stress:364,04±23,75ng/ml), in both groups PEA blunted the corticosteroneresponse tostress. PEA induced a decrease in basal D3R expressionand anincrease in TH expression in response to stress, bothresponseswere E2 dependent. No change was observed in D1R and D2Rexpression. We conclude that the neuroadaptiveresponse inducedby PEA in nucleus accumbens is under estrogeninfluence. Moreover,an altered stress response should be consideredbetweenthe neuroadaptive changes induced by PEA.