| First Author | Smits SM | Year | 2008 |
| Journal | Eur J Neurosci | Volume | 27 |
| Issue | 2 | Pages | 388-95 |
| PubMed ID | 18215235 | Mgi Jnum | J:132212 |
| Mgi Id | MGI:3775503 | Doi | 10.1111/j.1460-9568.2008.06032.x |
| Citation | Smits SM, et al. (2008) Alterations in serotonin signalling are involved in the hyperactivity of Pitx3-deficient mice. Eur J Neurosci 27(2):388-95 |
| abstractText | Pitx3 deficiency in mice causes a dramatic loss of dopaminergic neurones located in the substantia nigra pars compacta during development. This early disruption of the nigrostriatal pathway in Pitx3-deficient mice is characterized by increased spontaneous home-cage activity levels during the habitual sleep phase of these animals. These findings are reminiscent of the spontaneous hyperactivity in mice neonatally lesioned with 6-hydroxydopamine, which is caused by an extensive serotonergic hyperinnervation of the striatum. The present study investigated whether an imbalance between dopamine (DA) and serotonin (5-HT) signalling is involved in the behavioural phenotype of Pitx3-deficient mice. Serotonergic hyperinnervation was demonstrated by increased [3H]-citalopram autoradiographic binding specifically in the dorsal striatum of adult Pitx3-deficient mice, indicating alterations in 5-HT transporter levels that correlated to DA dysfunction in Pitx3 deficiency. In addition, stimulus-induced release of DA and 5-HT indicated an altered balance between these neurotransmitters in the dorsal striatum of Pitx3-/- mice. To determine whether the increased 5-HT signalling was involved in the spontaneous hyperactivity during the light phase observed in Pitx3 deficiency, we treated Pitx3-deficient and control mice with the selective irreversible tryptophan hydroxylase inhibitor p-chlorophenylalanine to decrease 5-HT levels. Reduction of 5-HT levels in Pitx3-deficient mice decreased their locomotor activity to normal levels, whereas the same treatment increased the locomotor activity levels of control mice. Taken together, our results indicate alterations in 5-HT signalling in Pitx3-deficient mice that underlie their spontaneous hyperactivity. |
