The effects of thioperamide on extracellular levels of glutamate and GABA in the rat prefrontal cortex.

RATIONALE

Histamine H3 receptors (H3R) are presynaptic heteroreceptors that negatively modulate the release of histamine and other neurotransmitters such as acetylcholine. Blocking H3 receptors with antagonists/inverse agonists has been shown to be procognitive and this effect has often been associated with increases in acetylcholine transmission. H3 receptors are abundantly expressed in the prefrontal cortex, an area associated with cognitive performance. While the procognitive effects of H3 receptor antagonists/inverse agonists may depend on alterations to acetylcholine or histamine release, other transmitters involved in cognitive processing such as glutamate and gamma-aminobutyric acid (GABA) may also be involved.

OBJECTIVE

The purpose of the present study was to examine the effects of thioperamide, an H3 receptor antagonist, on extracellular levels of glutamate and GABA in the prefrontal cortex.

MATERIALS AND METHODS

By means of in vivo microdialysis on freely moving Sprague Dawley rats, samples were collected and assayed via high-performance liquid chromatography coupled to electrochemical detection.

RESULTS

Replacement of calcium with magnesium revealed that the release of GABA, but not glutamate, was calcium-dependent. Thioperamide (10-20 mg/kg) did not affect basal glutamate or GABA release. Perfusion with a high concentration of potassium (100 mM) increased GABA, but not glutamate, release and thioperamide (20 mg/kg) attenuated the effects of high potassium on GABA release.

CONCLUSION

These data indicate that H3 receptors in the prefrontal cortex can enhance stimulated GABA release, but do not regulate basal levels of glutamate or GABA.