Reelin influences the expression and function of dopamine D2 and serotonin 5-HT2A receptors: A comparative study

- There is an increased D2 and 5-HT2A receptor density in HRM striatum.
- There is a decreased D2 and 5-HT2A receptor density in HRM frontal cortex.
- HRM showed increased D2 receptor functional activity in the striatum.
- HRM showed decreased 5-HT2A receptor functional activity in the frontal cortex.
- Reelin levels affect D2-5-HT2A receptor expression and function in a parallel way.

Reelin is an extracellular matrix protein that plays a critical role in neuronal guidance during brain neurodevelopment and in synaptic plasticity in adults and has been associated with schizophrenia. Reelin mRNA and protein levels are reduced in various structures of post-mortem schizophrenic brains, in a similar way to those found in heterozygous reeler mice (HRM). Reelin is involved in protein expression in dendritic spines that are the major location where synaptic connections are established. Thus, we hypothesized that a genetic deficit in reelin would affect the expression and function of dopamine D2 and serotonin 5-HT2A receptors that are associated with the action of current antipsychotic drugs.In this study, D2 and 5-HT2A receptor expression and function were quantitated by using radioligand binding studies in the frontal cortex and striatum of HRM and wild-type mice (WTM). We observed increased expression (p < 0.05) in striatum membranes and decreased expression (p < 0.05) in frontal cortex membranes for both dopamine D2 and serotonin 5-HT2A receptors from HRM compared to WTM.Our results show parallel alterations of D2 and 5-HT2A receptors that are compatible with a possible hetero-oligomeric nature of these receptors. These changes are similar to changes described in schizophrenic patients and provide further support for the suitability of using HRM as a model for studying this disease and the effects of antipsychotic drugs.