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Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance
F L R Lhullier1, R Nicolaidis, N G Riera
1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo), 90035, Pôrto Alegre, RS, Brazil. flrl@terra.com.br
Pharmacology, Biochemistry, and Behavior
|March 10, 2004
Summary
Dehydroepiandrosterone (DHEA) enhances memory in rodents by increasing glutamate release in the brain. This neurosteroid may strengthen glutamatergic signaling, impacting cognitive functions.
Area of Science:
- Neuroscience
- Endocrinology
- Pharmacology
Background:
- Dehydroepiandrosterone (DHEA) influences the central nervous system (CNS) via nongenomic actions.
- DHEA modulates neurotransmitter systems, including GABA(A), NMDA, and Sigma receptors.
- It exhibits neuroprotective properties and affects neuronal excitability and plasticity.
Purpose of the Study:
- To investigate DHEA's effects on glutamate release and uptake in the brain.
- To assess DHEA's impact on memory performance in an inhibitory avoidance task.
- To explore the relationship between DHEA, glutamatergic tonus, and memory.
Main Methods:
- In vitro and ex vivo studies on synaptosomal glutamate release and uptake.
- Intracerebroventricular and intraperitoneal administration of DHEA in rodents.
- Assessment of DHEA levels in serum and cerebrospinal fluid (CSF).
- Behavioral testing using an inhibitory avoidance task.
Main Results:
- DHEA significantly increased glutamate release in vitro (57%) and ex vivo (15% basal release).
- Intraperitoneal DHEA administration led to rapid increases in serum (33x) and CSF (21x) levels.
- DHEA administration improved memory performance in the inhibitory avoidance task.
Conclusions:
- DHEA enhances memory consolidation in an inhibitory avoidance task.
- The memory-enhancing effects may be linked to DHEA's ability to increase glutamate release.
- DHEA physiologically strengthens glutamatergic tonus, impacting cognitive function.