EFECTS OF THE CHRONIC TREAMENT WITH L-3,4- DIHIDROXYPHENYLALANINE(L-DOPA) ON THE NEUROENDROCRINE STRESS RESPONSE

SANTIAGO JORDI ORRILLO; MERCEDES IMSEN; LIZARRAGA MARIA ALFONSINA; ANA CLARA ROMERO

Mar Del Plata

Congreso; REUNIÓN ANUAL DE BIOCIENCIA 2019; 2019

SAIC, SAFE,SAB, SAP, AACyTAL, NANOMED-ar

0268 - EFFECTS OF THE CHRONIC TREATMENTWITH L-3,4-DIHYDROXYPHENYLALANINE (L-DOPA)ON THE NEUROENDOCRINE STRESS RESPONSESantiago Jordi ORRILLO (1) | Mercedes IMSEN(1) | AlfonsinaLIZARRAGA(1) | Ana Clara ROMERO(1) | Fernanda DE FINO(2) |Milagros PEÑA(3) | Alejandra ABELEDO MACHADO(3) | SandraZÁRATE(1) | Jimena FERRARIS(1) | Graciela DÍAZ-TORGA(3) |Daniel PISERA(1)INBIOMED-UBA-CONICET (1); INSTITUTO DEINVESTIGACIONES FARMACOLÓGICAS, UNIVERSIDAD DEBUENOS AIRES?CONICET (2); INSTITUTO DE BIOLOGÍA YMEDICINA EXPERIMENTAL (IBYME-CONICET) (3)Abstract/Resumen: Stress evokes a complex responsemediated by two systems: the hypothalamus-pituitary-adrenal(HPA) axis and the sympathetic-adreno-medullar (SAM) axis.Glucocorticoids and catecholamines secreted from the adrenalglands and sympathetic nerves are the main hormone effectorsof the physiological adaptations observed during stress.Moreover, prolactin (PRL) is another pituitary hormone secretedunder stressful stimuli. Catecholamines are synthesized from thehydroxylated precursor L-Dopa. This agent is also used withtherapeutic purposes, e.g. in Parkinson?s disease. In the presentresearch, we studied the effects of L-Dopa on the response to astressor. Adult male Wistar rats (300 g) were chronically treated(24 days) with LEBOCAR (L-Dopa (75 mg/day) - Carbidopa (7.5mg/day)) orally in drinking water and stressed by immobilizationduring the last 9 days of treatment. We first explored the activityof the SAM axis. Circulating noradrenaline increased in ratstreated with LEBOCAR (p<0.05; HPLC), while its content in theadrenals showed no significant alteration. Serum adrenaline (A)levels augmented by LEBOCAR treatment or stress (p<0.05;HPLC). Also, the adrenals from stressed animals showed highercontent of A (p<0.05). Next, we studied the reactivity of the HPAaxis. Chronically stressed rats displayed a lower ACTH secretion(ELISA) and a downregulation of POMC expression (qPCR) in theanterior pituitary (p<0.05). In addition, LEBOCAR treatmentinduced a reduction in serum ACTH and POMC levels (p<0.05).As expected, serum corticosterone (ELISA) peaked under chronicstress, an effect that was inhibited by treatment with LEBOCAR(p<0.05). Finally, pituitary PRL gene expression (qPCR) wasdownregulated by LEBOCAR treatment with a more pronouncedeffect when rats were also stressed (p<0.05). In summary, ourresults suggest that L-Dopa alters the neuroendocrine stressresponse by enhancing SAM axis activity and declining HPA axisreactivity and PRL expression.