Oral administration and behavioral testing of an inhibitor of serotonin synthesis

FOLTRAN, RB; HOCHT, C; TARAVINI, IRE; DIAZ SL

Mar del Plata

Congreso; XXXII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2017

Sociedad Argentina de Investigación en Neurociencia

Adult hippocampal neurogenesis can be enhanced by factors like serotonin (5-HT) depletion. Indeed, chronic administration of para-chlorophenylalanine (PCPA), an inhibitor of the 5-HT rate-limiting enzyme, results in increased survival of hippocampal newborn neurons, without affecting proliferation. We thus aim to dissect the role of 5-HT in the neurogenic multistep process, and in order to avoid intraperitoneal injections, experimental conditions for PCPA oral administration were set up. C57Bl/6J, male, 6-week old mice received PCPA (aprox. 200 mg/kg) by means of palatable yeast and jelly cubes, during 5 or 8 weeks. Brain and plasma samples were recovered to analyze 5-HT level. Neurogenic parameters were studied by immunohistochemistry and determined by unbiased stereologically counting. To study the role of PCPA-enhanced neurogenesis in the ability for pattern separation, we have previously performed 2 approachs: the Contextual fear discrimination learning test and the Object location task (OL). No difference were found between control and treated mice in any of these 2 tests. We now set up the Object Pattern Separation task, a recently developed test similar to the OL, but with more resolution. We suspect that this test may allow us to find subtle differences. These results will prove useful for a future proposal of replacement in the way of administration of PCPA and to implement this new test when studying animal models of enhanced neurogenesis.