Validation of a protocol for oral administration of PCPA, an inhibitor of serotonin synthesis

FOLTRAN, ROCÍO BEATRIZ; STEFANI, KAREN MELANY; HOCHT, C; DIAZ, SILVINA LAURA

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia, SAN; 2018

Sociedad Argentina de Investigación en Neurociencia, SAN

P244. Validation of a Protocol for OralAdministration of PCPA, an Inhibitor ofSerotonin SynthesisRocıo Beatriz Foltran1, Karen Stefani1,Christian H?ocht2 and Silvina Diaz11Inst. de Biologıa Celular y Neurociencias Prof. E. De Robertis,CONICET-UBA, Buenos Aires, Argentina2Ca´tedra de Farmacologıa, Fac. de Farmacia y Bioquımica, UBA,Buenos Aires, ArgentinaPresenting author: Rocıo Beatriz Foltran, rociobfoltran@gmail.comAdult hippocampal neurogenesis can be enhanced by factorsdepleting central serotonin (5-HT), like para-chlorophenylalanine(PCPA) that inhibits the 5-HT rate-limiting enzyme.Chronic PCPA intraperitoneal (i.p.) administration increasessurvival of newborn neurons, without affecting cell proliferation.Nevertheless, chronic i.p. injections affect animal welfare,as they are potentially painful. Thus, we designed andvalidated a protocol for PCPA oral administration. C57Bl/6Jmale mice received PCPA during 7 days via i.p. or by givingthe drug inside jelly cubes. 5-HT levels decreased about86.45% and 56.08% in the hippocampus of mice treatedwith oral and i.p PCPA, respectively, whereas in the prefrontalcortex, 5-HT levels decreased about 66.31% (oral) and49.14% (i.p.). Behavioral tests, like the Forced Swimming test(FST), the Nestlet shredding test (NST), and the MarbleBurying test (MBT) were performed. In the FST, micereceived fluoxetine i.p. 30 min before the test. PCPA-treatedmice spent significantly more time immobile than controls,revealing an effective reduction of 5-HT levels. While a tendencyto significantly increased shredding was seen in theNST, no difference was observed in the MBT. In a secondphase, mice received oral PCPA for 8 weeks, and survival ofnewborn cells was increased in the hippocampus of hyposerotonergic mice. Therefore, neurochemical, behavioral, and neurogenic results allow us to validate the protocol for oral administration of PCPA.