Related Experiment Video
Updated: Aug 8, 2026
Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
Phosphorylation of ERK and CREB in cultured hippocampal neurons after haloperidol and risperidone administration
Byung-Hwan Yang1, Hyeon Son, Seok Hyeon Kim
1Department of Neuropsychiatry, College of Medicine and Institute of Mental Health, Hanyang University, Seoul, Korea.
Abstract:
The purpose of the present paper was to determine whether the brief exposure of neurons to antipsychotic drugs is associated with the activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine 3',5'-monophosphate (cAMP) response element (CRE) binding protein (CREB). The activation of ERK-1/2 and CREB can be monitored by immunoblotting with antibodies that specifically recognize p-ERK-1/2 (phosphorylated on Thr-202 and Tyr-204) and p-CREB (phosphorylated on Ser-133). In hippocampal neuron cultures at 25 days in vitro (DIV), the levels of ERK and CREB phosphorylation significantly increased after treatment with haloperidol (50 nmol/L) and risperidone (50 nmol/L), except when risperidone was administered at the p-CREB level. However, risperidone also increased the p-CREB level at an insignificant rate in the same direction. At 10 DIV, none of the antipsychotic drugs significantly increased the level of ERK and CREB phosphorylation. The difference between levels of ERK and CREB phosphorylation in response to haloperidol and risperidone at 25 DIV was also observed. Risperidone significantly increased the level of ERK-1/2 phosphorylation, but not the level of CREB phosphorylation. Haloperidol, in contrast, had a different effect. These data indicate that neuronal maturation affects the phosphorylation of ERK and CREB in response to antipsychotic drugs. Furthermore, these results demonstrate that different antipsychotic drugs could lead to different profiles of ERK and CREB phosphorylation in neurons.
Insights
Antipsychotic drugs like haloperidol and risperidone activate ERK and CREB pathways in mature neurons. This drug effect on neuronal signaling depends on both drug type and neuronal development.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Extracellular signal-regulated kinases (ERK) and cyclic adenosine 3',5'-monophosphate (cAMP) response element (CRE) binding protein (CREB) are key signaling molecules in neurons.
- Understanding how antipsychotic drugs affect neuronal signaling pathways is crucial for treatment efficacy.
Purpose of the Study:
- To investigate if brief exposure to antipsychotic drugs activates ERK and CREB in neurons.
- To determine the role of neuronal maturation in the response to antipsychotic drugs.
Main Methods:
- Utilized hippocampal neuron cultures at different in vitro developmental stages (10 and 25 days in vitro).
- Administered haloperidol and risperidone at specific concentrations (50 nmol/L).
- Assessed the phosphorylation levels of ERK-1/2 and CREB using immunoblotting techniques.
Main Results:
- In mature neurons (25 DIV), both haloperidol and risperidone increased ERK-1/2 and CREB phosphorylation.
- Risperidone significantly increased ERK-1/2 phosphorylation but had a less significant effect on CREB phosphorylation.
- Immature neurons (10 DIV) showed no significant increase in ERK or CREB phosphorylation after drug treatment.
- Haloperidol demonstrated a different phosphorylation profile compared to risperidone.
Conclusions:
- Neuronal maturation significantly influences the phosphorylation response of ERK and CREB to antipsychotic drugs.
- Different antipsychotic drugs exhibit distinct effects on neuronal signaling pathways, impacting ERK and CREB phosphorylation.
- These findings highlight the importance of considering neuronal development and drug-specific mechanisms in antipsychotic action.
