Neurochemical, Behavioral, and Neurogenic Validation of a Hyposerotonergic Animal Model by Voluntary Oral Consumption of para-Chlorophenylalanine
| Autor: | Silvina L. Diaz, Karen M Stefani, Christian Höcht, Rocío B Foltran |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Fluoxetine Physiology business.industry Cognitive Neuroscience Cell Biology General Medicine Pharmacology Tryptophan hydroxylase Biochemistry Marble burying 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurochemical chemistry Oral administration Medicine Serotonin business Neurotransmitter 030217 neurology & neurosurgery 030304 developmental biology Behavioural despair test medicine.drug |
| Zdroj: | ACS Chemical Neuroscience. 11:952-959 |
| ISSN: | 1948-7193 |
| Popis: | The inhibitor of tryptophan hydroxylase, para-chlorophenylalanine (PCPA), has been classically employed as a pharmacological tool to deplete serotonin (5-HT) in animal models and to evaluate whether this neurotransmitter is involved in the action of pharmacological compounds. PCPA is usually administrated by intraperitoneal (ip) injections, which are stressful and painful. To avoid ip injections, we designed and validated a protocol for PCPA oral administration. C57BL/6 elite male mice received PCPA during 7 days either ip or by giving the drug inside jelly cubes at an estimated dose of 500 mg/kg on days 1 and 2 and 250 mg/kg for the rest of the treatment. 5-HT levels decreased by 85% and 55% in the hippocampus of mice treated with oral or ip PCPA, respectively, whereas in the prefrontal cortex, 5-HT levels decreased by 65% (oral) and 50% (ip). 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 ip 30 min before the test. In mice with oral PCPA treatment, fluoxetine did not induce significant reductions of immobility, indicating that reduction of 5-HT levels was effective. No effect of ip or oral 5-HT depletion was observed in the NST nor in the MBT. In a second experiment, mice received oral PCPA for 8 weeks: again, serotonin levels were significantly decreased in both hippocampus and cortex, and effects on hippocampal neurogenesis replicated previous observations in hyposerotonergic mice. Therefore, neurochemical, behavioral, and neurogenic results allow us to validate this refined protocol for voluntary oral consumption of PCPA. |
| Databáze: | OpenAIRE |
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