Prenatal Amphetamine-Induced Dopaminergic Alteration in a Gender- and Estrogen-Dependent Manner

PENNACCHIO, G. E.; SANTONJA, F. E.; NEIRA, F. J.; BREGONZIO, C.; SOAJE, M.

NEUROCHEMICAL RESEARCH

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2022 vol. 47 p. 1317 - 1328

0364-3190

Prenatal exposure to amphetamine induces changes in dopamine receptors in mesolimbic areas and alters locomotor responseto amphetamine during adulthood. Sex differences have been reported in amphetamine-induced brain activity and stresssensitivity. We evaluated the effects of prenatal amphetamine exposure on locomotor activity, dopamine receptors andtyrosine hydroxylase mRNA expression in nucleus accumbens and caudate-putamen in response to amphetamine challengein adult female and male rats. The role of estrogen in the response to restraint stress was analyzed in ovariectomized, prenatallyamphetamine-exposed rats. Pregnant rats were treated with d-amphetamine during days 15?21 of gestation. Nucleusaccumbens and caudate-putamen were processed for mRNA determination by real-time PCR. In nucleus accumbens, highermRNA dopamine (D3) receptor expression was found in basal and d-amphetamine-challenge conditions in female than male,and prenatal amphetamine increased the difference. No sex differences were observed in caudate-putamen. Basal salinetreatedfemales showed higher locomotor activity than males. Amphetamine challenge in prenatally amphetamine-exposedrats increased locomotor activity in males and reduced it in females. In nucleus accumbens, estrogen diminished mRNA D1,D2 and D3 receptor expression in basal, and D1 and D3 in ovariectomized stressed rats. Estrogen prevented the increasein tyrosine hydroxylase expression induced by stress in ovariectomized prenatally exposed rats. In conclusion, estrogenmodulates mRNA levels of D1, D2 and D3 receptors and tyrosine hydroxylase expression in nucleus accumbens; prenatalamphetamine-exposure effects on D3 receptors and behavioral responses were gender dependent.