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

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

Córdoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2018

Sociedad Argentina de Investigación en Neurociencias

Adult hippocampal neurogenesis can be enhanced by factors depleting central serotonin (5-HT), like para-Chlorophenylalanine (PCPA) that inhibits the 5-HT rate-limiting enzyme. Chronic PCPA intraperitoneal (i.p.) administration increases survival of newborn neurons, without affecting cell proliferation. Nevertheless, chronic i.p. injections affect animal welfare, as they are potentially painful. Thus, we designed and validated a protocol for PCPA oraladministration. C57Bl/6J male mice received PCPA during 7 days via i.p. or by giving the drug inside jelly cubes. 5-HT levels decreased about 86,45% and 56,08% in the hippocampus of mice treated with oral and i.p PCPA respectively, whereas in the prefrontal cortex, 5-HT levels decreased about 66,31% (oral), and 49,14% (i.p.). Behavioral tests, like the Forced Swimming test (FST), the Nestlet shredding test (NST), and the Marble Burying test (MBT) were performed. In the FST, mice received fluoxetine i.p. 30 min before the test. PCPA-treated mice spent significantly more time immobile than controls, revealing an effective reduction of 5-HT levels. While a tendency to significantly increased shredding was seen in the NST, no difference was observed in the MBT. In a second phase, mice received oral PCPA for 8 weeks, and survival of newborn 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.