Different sensitivity to anesthesia according to ECoG data in dopamine transporter knockout and heterozygous rats

• Published in: Neuroscience letters Vol. 788; p. 136839
• Main Authors: Belov, Dmitry, Fesenko, Zoia, Efimov, Andrey, Lakstygal, Anton, Efimova, Evgeniya
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25-09-2022
• Subjects: Anesthesia; Delta rhythm; Dopamine transporter; Electrocorticogram; Gamma rhythm; Knockout rats; Dopamine transporter; Anesthesia; Delta rhythm; Electrocorticogram; Knockout rats; Gamma rhythm
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2022.136839

•Dopamine transporter knockout rats have increased levels of the extracellular dopamine.•Under anesthesia, the electrocorticogram of knockout rats differs from wild type.•Moderate potentiation of the dopamine system in heterozygotes disrupts the sedation.•In total knockouts, greater potentiation of the dopamine system enhances sedation.•The total knockouts showed decreased spatial synchronization in the gamma range.
Dopamine in the brain is involved in many important functions, including the regulation of wakefulness. There is also some evidence suggesting that the dopamine function is crucial in anesthetic function. The state of anesthesia is characterized by a change in the level of consciousness and a change in brain electrical activity.
Due to impaired mechanisms of dopamine transportation back to the synaptic terminal, dopamine transporter (DAT) knockout and heterozygous rats have increased levels of the extracellular dopamine. In our work, we registered ECoG disturbances in knockout and heterozygous rats, as well as disturbances in tone and activity in acute experiments under the anesthesia Zoletil (tiletamine and zolazepam) from the somatosensory cortex using a NeuroNexus flat multielectrode array to study gamma activity. We also used four low-resistance electrodes to control the slow rhythm.
Both low-resistance and high-resistance electrodes showed differences in the ECoG spectrum of heterozygotes and total knockouts from the wild type and from each other. Heterozygous rats for the DAT gene (HET) showed increased rapid beta and gamma activity and decreased slow delta activity, while complete knockouts (KO), on the contrary, showed increased delta activity and decreased beta and gamma activity. Thus, the ECoG spectrum of HET is shifted to the right, while that of KO is shifted to the left. Full knockouts also showed decreased spatial synchronization in the 30–100 Hz gamma range compared to the wild type (WT).
It is assumed that sedation of HET and KO is shifted towards opposite directions compared to WT under the same anesthesia conditions.