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Extracellular Recording of Neuronal Activity Combined with Microiontophoretic Application of Neuroactive Substances in Awake Mice
Published on: May 21, 2016
Dopamine prevents muscarinic-induced decrease of glutamate release in the auditory cortex
M Atzori1, P O Kanold, J C Pineda
1University of Texas at Dallas, School for Behavioral and Brain Sciences, Richardson, 75080, USA. marco.atzori@utdallas.edu
Novel stimuli release acetylcholine and dopamine, impacting glutamate release. Antipsychotic drugs may act by modulating these neurotransmitters, potentially offering a dual therapeutic mechanism in the auditory cortex.
Area of Science:
- Neuroscience
- Neuropharmacology
- Auditory Cortex Research
Background:
- Acetylcholine and dopamine are co-released in the cortex during novel stimuli.
- Acetylcholine reduces glutamate release via presynaptic muscarinic receptors.
- Dopamine's role in modulating this cholinergic effect is under investigation.
Purpose of the Study:
- To investigate the interaction between acetylcholine and dopamine on glutamate release in the auditory cortex.
- To explore the potential mechanism of action of antipsychotic drugs on glutamatergic neurotransmission.
Main Methods:
- Recording evoked excitatory postsynaptic currents in auditory cortex neurons.
- Utilizing oxotremorine to activate muscarinic receptors.
- Assessing the effects of dopamine and antipsychotic drugs (haloperidol, clozapine, lamotrigine) on glutamatergic currents.
Main Results:
- Oxotremorine reduced glutamatergic current amplitude, an effect abolished by dopamine.
- This suggests dopamine hypersensitivity, as seen in schizophrenia, might impair cholinergic-induced glutamate reduction.
- Antipsychotics restored muscarinic modulation and directly reduced glutamatergic currents.
Conclusions:
- Presynaptic modulation of glutamate release by acetylcholine and dopamine is crucial in the auditory cortex.
- Antipsychotic drugs exhibit a dual action: dopamine receptor antagonism and direct depression of glutamatergic currents.
- This dual action provides a potential mechanism for antipsychotic efficacy, possibly through modulating glutamatergic signaling.
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