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ANESTHETIC PHARMACOLOGY

In Vivo Dopamine Measurements in the Nucleus Accumbens After Nonanesthetic and Anesthetic Doses of Propofol in Rats

Laure Pain, MD^*, Serge Gobaille, BR, Carmen Schleef, BR, Dominique Aunis, PhD, and Philippe Oberling, MD PhD^||

*Hôpitaux Universitaires de Strasbourg; U405 INSERM; IFR Neurosciences 37; INSERM U338; and ||Department of Physiology, Institut de Physiologie, Université Louis Pasteur, Strasbourg, France

Address correspondence and reprint requests to Dr. Laure Pain, Department of Psychology, 2 Colchester Ave., University of Vermont, Burlington, VT 05405. Address e-mail to Laurepain{at}aol.com

There is growing evidence that propofol acts on affective and reward processes. We designed this study to assess the effect of propofol on the concentration of dopamine in the nucleus accumbens, a main component of the mesolimbic system. The concentration of dopamine in the nucleus accumbens was assessed by using in vivo brain microdialysis in freely moving rats. A microdialysis probe was placed within guide cannulae previously placed during stereotaxic surgery. Fluid was perfused through the probe, and samples were collected every 20 min for measuring concentrations by high-pressure liquid chromatography. All rats served as their own controls and were randomized to four different doses of propofol, injected intraperitoneally: 0, 9, 60, or 100 mg/kg, according to a within design. Compared with the baseline value, dopamine concentration was decreased at the smallest dose of 9 mg/kg, whereas concentration was largely increased at the subanesthetic (60 mg/kg) and anesthetic (100 mg/kg) doses. This increase was of the same magnitude (+90%) for subanesthetic and anesthetic doses but was more prolonged at the anesthetic dose. Data show that only subanesthetic and anesthetic doses of propofol increase the concentration of dopamine in the nucleus accumbens, as previously described with drugs of potential abuse.

IMPLICATIONS: Depending on the dose, propofol either increased or decreased the concentration of dopamine in the nucleus accumbens, as assessed during microdialysis in freely moving rats. Only large doses which display a pharmacological profile, such as propofol, may show promise.

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