Role of brain-derived neurotrophic factor in the control of D3 receptor expression

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments

“…Recently, we provided evidence indicating that brain-derived neurotrophic factor (BDNF), a neurotrophin synthesized by dopamine neurons, 59 anterogradely transported and released by neurons upon depolarization, 60 is the factor controlling D 3 receptor expression. 61 In agreement with this contention, BDNF expression is reduced by stress 62 and elevated by chronic antidepressant treatments. 63 In conclusion, our study suggests that D 3 receptor expression and function are down-regulated in stress and, possibly, depression, and that these changes are reversed by antidepressant treatments.…”

Brain Derived Neurotrophic Factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia

“…12 In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. 13 In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) 14 between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neurolepticresponding patients and in non-substance-abusing patients.…”

“…The analysis of the respective effect of DRD3 BalI polymorphism and BDNF alleles indicates that each of these genetic markers is independently associated with therapeutic response in schizophrenia. Since BDNF presumably controls DRD3 gene expression, 13 it is conceivable that alterations in the function of each gene independently contribute to a DRD3 over-expression, which was found in post-mortem brain of patients with schizophrenia. 22 The association of variants of each of these genes with the therapeutic response in schizophrenia is indeed consistent with the fact that antipsychotic drugs act at the DRD3, 23 and may therefore normalize the transmission through this receptor in the subset of treatment-sensitive patients.…”

Dopamine D3Receptors Expressed by All Mesencephalic Dopamine Neurons

“…The first is expressed by non-dopaminergic neurons, which are the most abundant in the SN pars lateralis and also contain the highest levels of D 3 R mRNA. This suggests that a large fraction of D 3 R gene transcripts are expressed by non-dopaminergic neurons, which may be liable to downregulation of D 3 R expression after dopamine neuron denervation by 6-hydroxydopamine (Sokoloff et al, 1990), similar to that occurring in the nucleus accumbens (Lévesque et al, 1995) as a result of BDNF deprivation (Guillin et al, 1999). It remains to be determined whether the putative downregulation of D 3 R expression in non-dopaminergic mesencephalic neurons after dopamine neuron ablation also results from the loss of BDNF, as is the case of striatal neurons (Guillin et al, 1999), or from the loss of another factor.…”

“…We originally proposed the existence of D 3 autoreceptors on the basis of the expression in substantia nigra (SN) and VTA of D 3 R mRNA, which strongly decreases after lesion of dopamine neurons (Sokoloff et al, 1990). This lesion, however, also downregulates postsynaptic D 3 R in AccSh (Lévesque et al, 1995), by deprivation of brain-derived neurotrophic factor (BDNF), an anterograde factor of dopamine neurons (Guillin et al, 1999). Hence the lesion-induced decrease in SN/VTA could reflect a similar process occurring in nondopaminergic neurons.…”