In the course of work on the behavioral
effects of the intraventricular administration
of nonneurotoxic doses of kainate, an agonist of
the "glutamate-preferring" receptor, we noticed
that kainate suppressed the appearance of
stretching and yawning (SY) in rats. This
was most obvious with repeated exposure to the
observation apparatus. The number of SY emitted
by normal and saline-injected animals increases
with repeated exposures to the observation
boxes. By the third or fourth exposure, SY
reaches a plateau of seven to eight SY in the
hour observation period. Low doses of kainate
completely suppressed SY.
Our interest in finding behavioral correlates
of changes in glutamate-mediated
neurotransmission led us to examine the effect
of glutamate antagonist on the occurrence of SY.
We now present our findings using glutamate
diethyl ester (GDEE), an antagonist of glutamate
and aspartate.
Materials and Methods
The subjects were 23 male Long-Evans hooded
rats (225-300g). GDEE was rernoved from a
freezer and dissolved in saline (0. 15 mmol/mI
for the lowest dose and 1 mmol/ml for the rest).
GDEE was injected IP within 15 min after it was
removed from the freezer so that it had little
opportunity to undergo hydrolysis. GDEE was
given in doses of 0.15 mmol/kg (N = 5), 1
rnmol/kg) (204mg/kg) (N = 3), 3 mmol/kg (N = 7),
and 4.5 mmol/kg (N = 3). Five more rats were
injected with 1 ml/kg of saline.
Immediately after injection the subiects were
placed in individual observation boxes
(30x3Ox2Ocm) as described previously. Up to live
animals were observed at one time. SY was
recorded for 1 h (six 10-min periods). For the
five rats administered 0.15 mmol/kg GDEE,
grooming was also recorded for the last 50 min
of the session. Grooming was scored in the
manner of Gispen et al. (1975).
Results
The systemic injection of GDEE in these doses
resulted in the rapid onset (less than 10 min
after injection) of very pronounced
stretching activity. Stretches were often
seen immediately succeeding one another (a
"stretching crisis") at the three higher doses.
At doses of 0. 15, 1, 3, and 4.5 mmol/kg of
GDEE, the mean number of SY induced in 1 h were
13.2, 27, 34.7, and 40, respectively. Saline
injection resulted in the occurrence of 1.5 SY
in an hour. This was recorded as six 10-min
periods and is shown in Fig. The declines of SY
in the fifth period for the three higher doses
and the sixth period for the 1 mmol/kg group
were concomitant with the subjects lying down.
They appeared to be asleep.
Out of a total of over 400SY recorded after
administration of the three higher doses of
GDEE, yawns accotinted for less than 1 of the
total. At the 0.15mmol/kg dose, yawns were
commonly observed and accompanied a majority of
the stretches. There were also more stretches of
the front limbs occurring after the lowest dose
of GDEE.
At the 0. 15 mmol/kg dose grooming was
counted. The mean score (25.2 out of a possible
200) was well within the normal reported
range.
Discussion
The administration to rats of GDEE, an
antagonist of both glutamate and aspartate
receptors, results in the occurrence of the
stretching and yawning syndrome (SYS). Coupled
with our previous findings that kainate
suppresses naturally occurring SY, the
present results suggest a role of
glutamate-mediated transmission in the emission
of SY. SY can be induced by a variety of
chemical agents. These include
adrenocorticotrophic hormone (ACTH) and
melanocyte-stimulating hormone (MSH) (Ferrari et
al., 1963; Izumi et al., 1973; Gispen et al.,
1975), zinc (Izumi et al., 1973), recovery from
potassium chlorideinduced cortical spoading
depression (Huston, 1971), and muscarinic
stimulants (Urba-Holmgren et al., 1977). ACTH
and GDEE induce an SY pattern in which one
stretch may immediately succeed another. Ferrari
et al. (1963) termed this pattern a "crisis".
Unlike ACTH, however, GDEE does not induce
excessive grooming. This difference helps to
confirm the suggestions by Gispen et al. (1975)
and Colbern et al. (1977) that the neural
mechanisms of SY are different from those
mediating excessive grooming.
