RT Journal Article
SR Electronic
T1 Genotype-Dependent Activity of Tryptophan Hydroxylase-2 Determines the Response to Citalopram in a Mouse Model of Depression
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8165
OP 8172
DO 10.1523/JNEUROSCI.1816-05.2005
VO 25
IS 36
A1 Luigi Cervo
A1 Alessandro Canetta
A1 Eleonora Calcagno
A1 Silvia Burbassi
A1 Giuseppina Sacchetti
A1 Silvio Caccia
A1 Claudia Fracasso
A1 Diego Albani
A1 Gianluigi Forloni
A1 Roberto W. Invernizzi
YR 2005
UL http://www.jneurosci.org/content/25/36/8165.abstract
AB 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.