Beta and gamma range EEG power-spectrum correlation with spiking discharges in DBA/2J mice absence model: role of GABA receptors.
OBJECTIVE
To describe the correlations between spiking pattern and EEG power spectrum frequency in DBA/2J mice, a model for murine absence seizures, after gamma-aminobutyric acid (GABA)(B) modulation.


METHODS
The animals were first tested with the GABA(B) agonist l-baclofen followed by the GABA(B) antagonist SCH 50911. Moreover, digital EEGs recorded under experimental conditions were processed at baseline and 10 and 20 min after l-baclofen injection. This procedure was followed by injection of the GABA(B) antagonist SCH50911 and by an additional EEG evaluation at 10 and 20 min from drug administration. The power spectra analysis of signals was obtained for delta (0.5-3 Hz), theta (3.5-7.5 Hz), alpha (8-12 Hz), beta (13-20 Hz), and gamma (21-50 Hz) frequencies.


RESULTS
The spiking pattern and power spectrum of beta activity was increased by <or=80% after administration of 5 mg/kg l-baclofen, whereas gamma power frequency decreased to the same extent. After administration of 50 mg/kg SCH 50911, spiking activity and beta power frequencies were markedly reduced (>80%), whereas gamma power increased (correlation, 0.92; p < 0.001). The remaining frequency bands were unaffected.


CONCLUSIONS
This study confirms the potential of GABA(B) antagonists in contrasting seizure absence in rodent models and suggests the application of drugs with a similar mechanism in humans. In addition, because GABA(B) antagonists not only contrast seizure in rodent models of absence but also improve "cognitive" performance, it could be hypothesized that gamma increase, correlated with optimized cortical binding during coherent percepts, may produce potential cognition-enhancing effects.
Marrosu
Francesco
F
Dipartimento di Scienze Neurologiche e Cardiovascolari, Università di Cagliari, Monserrato, Italy. marrosu@unica.it
Santoni
Federico
F
Fà
Mauro
M
Puligheddu
Monica
M
Barberini
Luigi
L
Genugu
Fabrizio
F
Frau
Roberto
R
Manunta
Mario
M
Mereu
Giampaolo
G
D000513:Alpha Rhythm / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001611:Beta Rhythm / Q000187:drug effects; D002540:Cerebral Cortex / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003344:Cortical Synchronization / Q000187:drug effects; D003700:Delta Rhythm / Q000187:drug effects / Q000706:statistics & numerical data; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data*; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000503:physiopathology*; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000502:physiology
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018755:GABA Agonists; D018756:GABA Antagonists; D009025:Morpholines; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen