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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201-209 9
