EXTRACELLULAR DOPAMINE AND GABA CONCENTRATIONS IN THE NIGRASTRIATAL SYSTEM AND THALAMUS OF RATS UNDER PROPOFOL ANESTHESIA

Abstract

S502 Many reports have suggested that enhancement of the inhibition (GABA (A-mediated)) or depression of excitatory (glutamate-mediated) neurotransmission, or both, may account for the dominant depressant effects of anesthetics on the central nervous system. Recently, several studies have implied that propofol may interact with dopamine receptors [1,2]. However, there is no evidence that propofol alters the release of dopamine and GABA. Therefore, the goal of this study is to examine the effects of propofol on the concentrations of dopamine and GABA in the nigrostriatal system and thalamus by using in vivo microdialysis. Materials and methods: Sprague-Dawley female rats weighing 200-250 g (n=36) were randomly assigned to two groups: group C (n=18) were free moving rats serving as controls and the microdialysis probe was implanted in the striatum (S) (n=6), the substantia nigra (SNR) (n=6) or ventrolateral thalamus (VL)(n=6). Group Propofol (P) rats (n=18) were anesthetized with propofol at a 50 mg/kg/hour infusion rate and the probes were in the same brain parts as described above (n=6 each). Microdialysis probes (CMA PC12, length 1mm for SN or VL, and 2mm for S) were stereotactically implanted in the left S, SNR or VL of each rat. Group C rats were prepared for implantation of microdialysis probe guide cannula under isoflurane anesthesia on day 1. On day 2, probes were inserted into each part described above. After 2 hours recovery, the five dialysates were sampled every 10 min (perfusion rate 1.0 [micro sign]l/min). In group P, 2 hours' administration of propofol after probe implantation was followed by five consecutive samplings. Dialysates were analyzed by HPLC. Each concentration was corrected according to the recovery rate of each probe. Data were analyzed by Mann-Whitney tests and are presented as means +/- SD. P<0.05 was considered statistically significant. Results: Physiological parameters (blood pressure, body and brain temperatures, etc.) did not differ significantly between the two groups. In group C, baseline concentrations of dopamine were 16.4 +/- 1.4nM (S), 3.1 +/- 0.2nM (SNR) and 8.0 +/- 0.3nM (VL) and GABA concentrations were 215.2 +/- 9.3nM (S), 80.0 +/- 3.3nM (SNR) and 45.9 +/- 3.4nM (VL), respectively. In group P, propofol decreased the dopamine by 21% (p<0.005) in VL. However, it increased the dopamine by 233% (p<0.005) in SNR. Propofol increased GABA by 199% (p<0.005) and 229% (p<0.005) in SNR and VL, respectively. There were no significant dopamine or GABA concentration changes in S. Discussion: A large dose of propofol stimulated dopaminergic fibers or inhibited uptake of dopamine in the nigrostriatal system. Propofol also increased GABA concentrations in SNR and VL. The increase in the dopamine concentration in SNR is suspected to be one of the mechanisms by which propofol induces involuntary movement. These results may explain why propofol has not only hypnotic effect, also has an anesthetic property.