Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression
| العنوان: | Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression |
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| المؤلفون: | Luigi Cervo, Diego Albani, Silvio Caccia, Roberto W. Invernizzi, Eleonora Calcagno, Silvia Burbassi, Claudia Fracasso, Gianluigi Forloni, Alessandro Canetta, Giuseppina Sacchetti |
| المصدر: | The Journal of Neuroscience. 25:8165-8172 |
| بيانات النشر: | Society for Neuroscience, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, Serotonin, medicine.medical_specialty, Genotype, Citalopram, Motor Activity, Tryptophan Hydroxylase, Pharmacology, Polymerase Chain Reaction, Mice, Neurochemical, Species Specificity, Neurobiology of Disease, Internal medicine, medicine, Animals, Swimming, DNA Primers, Mice, Inbred BALB C, Polymorphism, Genetic, Depression, Chemistry, General Neuroscience, Tryptophan, Tryptophan hydroxylase, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, Mice, Inbred DBA, Antidepressive Agents, Second-Generation, Antidepressant, Reuptake inhibitor, Behavioural despair test, medicine.drug |
| الوصف: | Polymorphism of tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of brain serotonin (5-HT), is associated with less synthesis of brain 5-HT in DBA/2J and BALB/c than in C57BL/6J and 129/Sv mice. We selected the forced swimming test, a mouse model used to assess the antidepressant potential of drugs, and neurochemical techniques to study strain differences in the response to citalopram, a selective 5-HT reuptake inhibitor. Citalopram reduced immobility time in C57BL/6J and 129/Sv mice but had no such effect in DBA/2J and BALB/c mice. The drug reduced accumulation of 5-hydroxytryptophan (5-HTP), an indicator of 5-HT synthesis, in C57BL/6J and 129/Sv mice but much less in DBA/2J and BALB/c mice. Pretreatment with tryptophan raised 5-HTP accumulation and reinstated the antidepressant-like effect of citalopram in DBA/2J and BALB/c mice, whereas pharmacological inhibition of 5-HT synthesis prevented the effect of citalopram in C57BL/6J and 129/Sv mice. Because there were no strain differences in catecholamine synthesis, locomotor activity, and brain levels of citalopram at the end of the behavioral test, the results suggest that the failure of citalopram to reduce immobility time in DBA/2J and BALB/c mice is attributable to genotype-dependent impairment of 5-HT synthesis. Interstrain comparisons could probably be a useful strategy for understanding the mechanisms underlying the response to selective serotonin reuptake inhibitors. |
| تدمد: | 1529-2401 0270-6474 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::595290ba580c2055dfb40e490dfd7c3aTest https://doi.org/10.1523/jneurosci.1816-05.2005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....595290ba580c2055dfb40e490dfd7c3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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