CONICET | Buscador de Institutos y Recursos Humanos

Dysregulation of dopamine transmission contributes to several neurological disorders including addiction and schizophrenia. Nowadays, the use of D2 receptor ligands to treat these disorders is widely used. D2 dopamine receptors are expressed as postsynaptic receptors and as presynaptic autoreceptors. For the last three decades many efforts have been taken into elucidate the precise role of D2 dopamine autoreceptors at regulating dopamine transmission. It is well established now that dopamine release from dopamine neurons can be modulated by several factors. Activation of dopamine autoreceptors located at the soma level decreases the firing rate of dopaminergic neurons. Dopamine D2 autoreceptors regulate dopamine release as well as dopamine synthesis. In addition, the introduction of D2 null mutant mice allowed the study of the regulation of dopaminergic transmission by these receptors although without presynaptic selectivity. Some groups using these lines of mice have proposed that long-term adaptations occur in dopamine release and uptake in response to the lack of both postsynaptic and presynaptic D2 activity. The aim of this study is to determine for the first time the level of significance of D2 autoreceptor regulation on central dopaminergic system and to evaluate behavioral and neurochemically the consequences of the loss of presynaptic D2 autoreceptors.