Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats.
Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.
Dirksen
R
R
Department of Anesthesiology, University of Nijmegen, The Netherlands. R.DIRKSEN@ANES.AZN.NL
Ellenbroek
B
B
van Egmond
J
J
Cools
A R
AR
D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018686:Anesthetics, Intravenous; D005680:gamma-Aminobutyric Acid; D001058:Apomorphine; D015742:Propofol