mise à jour du
20 novembre 2005
1989; 97; 275-276
Discrepancy in the time course of EMD 23448 induced yawning and reduction of extracellular dopamine
Lars Stahle and Urban Ungerstedt
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden


Yawning behaviour induced by dopamine agonists was originally suggested to be mediated by stimulation of dopamine autoreceptors (Mogilnicka and Klimek 1977; Yamada and Furukawa 1980), i.e., by stimulating dopamine autoreceptors the release of dopamine would be inhibited and yawning would appear as an indirect consequence of the reduced dopaminergic transmission. However, recent findings have suggested that yawning may not be mediated by autoreceptors (Morelli et al. 1986; Serra et al. 1986; ScheelKruger 1986; Stahle 1987; Stahle and Ungerstedt 1988). In this study we further investigate the hypothesis that yawning is related to a reduction of the release of dopamine by studying the time-course of yawning and reduction of extracellular levels of dopamine as measured by microdialysis (Ungerstedt 1984) following treatment with the partial dopamine agonist EMD 23448 (Seyfried et al. 1982).
A guide cannula was implanted stereotaxically such that a microdialysis probe (Carnegie Medicin, Stockholm, Sweden) inserted 2 days later in the awake rat would be situated in the striatum (see Stahle and Ungerstedt). The 3.0 x 0.5 mm dialysis probe was perfused with a Ringer solution at a flow of 2.0 pi/min and fractions were collected every 20 min (40 VI). The samples were assayed for dopamine, DOPAC, HVA and 5-HIAA by HPLC with electrochemical detection (Sharp et al. 1986). Two hours after implantation and when a steady baseline of dopamine was obtained, 2 mg/kg EMD 23448 was injected subcutaneously. Yawning was registered by direct observation.
The results are summarised in Fig. 1. Yawnings appears shortly after injection and the peak number of yawnings was obtained in the first 20 min. After 60 min no more yawnings were observed. Extracellular levels of dopamine did not decrease in the first 20-min fraction. The levels of dopamine were reduced to a minimum of 60% of baseline 40-60 min after injection and recovered slowly during the following hour (Fig. 1). DOPAC and HVA were reduced to 75% of baseline, with minimum levels attained after 60-80 min (data not shown).
The present findings indicate that there is a discrepancy in the time-course of EMD 23448-induced yawning and reduction of extracellular levels of dopamine. This finding suggests that the mechanisms behind these two effects of a dopamine agonist are different and, in particular, that a causal relation between reduction of dopamine release and yawning is less likely. This interpretation is based on
the hypothesis that changes in the extracellular levels of dopamine as measured by microdialysis reflects changes in the release of dopamine. This hypothesis is supported by pharmacological and physiological evidence (Ungerstedt 1984; Westerink et al. 1987).
It is concluded that the time-course of EMD 23448-induced yawning and reduction of extracellular dopamine levels are different, supporting the notion that yawning is not a dopamine autoreceptor-mediated phenomenon. It is suggested that yawning is mediated by a sensitive population of post-synaptically located dopamine receptors.
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