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Morphometric study of synaptic patterns in the rat caudate nucleus and hippocampus under haloperidol treatment
N A Uranova1, D D Orlovskaya, K Apel
1Laboratory of Clinical Neuromorphology, All-Union Center of Mental Health, Moscow, Soviet Union.
Insights
Chronic haloperidol treatment significantly alters synapse structure in rat caudate nucleus, increasing synaptic density and modifying synaptic parameters. These changes may underlie behavioral supersensitivity and dopamine D2 receptor upregulation.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Dopamine D2 receptors are crucial in regulating neuronal function.
- Antipsychotic drugs like haloperidol target these receptors.
- Understanding drug-induced synaptic plasticity is key to explaining therapeutic and side effects.
Purpose of the Study:
- To investigate the ultrastructural changes in synapses within the rat caudate nucleus and hippocampus.
- To correlate these morphological alterations with chronic haloperidol administration.
- To explore the relationship between synaptic changes and dopamine D2 receptor upregulation.
Main Methods:
- A morphometric analysis of synapses was conducted on electron micrographs.
- Synapses on dendritic shafts and spines were examined in the caudate nucleus and hippocampus.
- Quantitative measurements of synaptic parameters were performed under chronic haloperidol treatment.
Main Results:
- In the caudate nucleus, chronic haloperidol increased synaptic density on dendritic shafts (83%) and spines (53%).
- Axospinous synapses showed increased presynaptic terminal area, mitochondria, and postsynaptic density.
- Synapses on dendritic shafts exhibited decreased presynaptic terminal and mitochondria area but increased active zone length.
Conclusions:
- Chronic haloperidol treatment induces significant, region-specific synaptic plasticity in the caudate nucleus.
- Observed morphological changes in synapses correlate with behavioral supersensitivity.
- The findings support the role of synaptic remodeling in dopamine D2 receptor upregulation and antipsychotic drug effects.
Abstract:
A morphometric study of the synapses on dendritic shafts and spines was performed in the rat caudate nucleus and the CAI area of the hippocampus under chronic haloperidol treatment. In the nucleus caudatus, the synaptic density on dendritic shafts increased by 83% and those on spines by 53%. Most of the parameters measured in axospinous synapses were significantly increased: the area of presynaptic axon terminals (20%), the number of mitochondria per axon terminal (51%), the length of active zone (11%), the area of postsynaptic density (23%), and the perimeter of postsynaptic density (12.5%). The area of postsynaptic spines showed no changes. In the synapses on dendritic shafts, the area of presynaptic terminals decreased (31%), the area of mitochondria per terminal decreased (40%), the length of active zone increased (14%), and other parameters were unchanged. There were no significant differences in the same parameters measured in the hippocampus. The data are discussed as morphological correlates of behavioral supersensitivity and dopamine D2 receptor up-regulation.