title: Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia.
abstract: BACKGROUND
  A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia.
  
  
  METHODS
  In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose-response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiologic changes induced by chloro-APB and quinpirole during isoflurane general anesthesia.
  
  
  RESULTS
  Chloro-APB decreased median time to emergence from 330 to 50 s. The median difference in time to emergence between the saline control group (n = 6) and the chloro-APB group (n = 6) was 222 s (95% CI: 77-534 s, Mann-Whitney test). This difference was statistically significant (P = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram δ power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia.
  
  
  CONCLUSIONS
  Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia and produces behavioral and neurophysiologic evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general anesthesia.
authors.affiliation: Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Taylor
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chemali
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
mesh_terms: D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D019257:Quinpirole; D007530:Isoflurane