Introduction : Experiments
involving REM sleep deprivation (REMSD),
employing the water tank technique (Jouvet et
al., 1964). have shown that this procedure is
able to alter some behaviors that can be induced
by drugs acting on many neurotransmitter
systems. For instance, it has been demonstrated
that rats submitted to REMSD for 96 hr show an
augmented response to postsynaptic doparnine
(DA) agonists as indicated by an intensification
of aggressiveness, stereotypy and rearing
induced by apomorphine (Tufik 1978; Mogilnicka
1981). These findings are analogous to that
obtained with chronic haloperidol treatment,
suggesting that both procedures induce a state
of postsynaptic doparninergic supersensitivity
(Gianutsos 1974: von Voigtlander 1975, Tufik
1981).
Several evidences exist that drug-induced
yawning in rats is a behavioral consequence of
dopaminergic autoreceptor stimulation. resulting
in decrease of DA synthesis and release,
impairment of doparninergic transmission and
consequent removal of the inhibition that DA
neurons exert upon cholinergic neurons
(Yamada
and Furukawa 1980, 1981 Ushijima
1984). Thus, yawning behavior seems to
involve both dopaminergic inhibition and
cholinergic activation.
A previous study from our laboratory has
demonstrated that REMSD significantly decreases
the yawning response by presynaptic doses of
apomorphine and by small doses of physostigmine
and pilocarpine suggesting that this procedure
induces subsensitivity of presynaptic dopamine
and postsynaptic acetylcholine receptors (Tufik
1987).
The aim of the present study is to verify the
response of the doparninergic and cholinergic
systems after 24 hr following the 96 hr period
of REM sleep deprivation. Looking at the
recovery process of these systems after a
resting period, we expect to gather information
about the mechanisms underlying the effects of
REM sleep deprivation. [...]
Discussion : We previously reported
thal rats exposed to REMSD are less sensitive to
induction of yaning by presynaptic doses of
apomorphine, physostigmine or pilocarpine (Tufik
1987). In the present study we examined the
effects of these drugs on yavvning in rats
submitted to the same period of REMSD, but
allowed to recover for 24hr. After the 24hr
recovery period, yawning induced by apomorphine
was still reduced. whereas pilocarpine-induced
yawning had returned to control levels.
Physostigmine-induced yawing was found
inhibited only at the lowest dose studied. Thus,
it seems that these distinct response to
dopaminergic and cholinergic drugs disclose a
distinct action ofthe REMSD on these
systems.
A doparninergic-cholinergic link bas been
postulated in some brain areas, namely the
nigrostriatal and septo-hippocampal pathways,
where dopaminergic neurons exert an inhibitory
role upon cholinergic neurons (Yamada and
Furukawa, 1980, 1981 ). Both areas have been
implicated in the elicitation of yawning (Yamada
1986). Chronic interruption of DA transmission,
through repeated injections of haloperldol
(Gianutsos and Lal, 1976) or treatment with
6OH-dopamine (Kato 1978) elicits a cholinergie
hyposensitivity as a consequence of the
hyperactivity of cholinergic neurons free from
dopaminergic inhibition. These facts could
explain the inhibitory effect upon apomorphine
andphysotogmine induced yawning produced by
chronic haloperidol (Ushijima l984) but do not
explain why pilocarpine-induced yawning was
found unaltered in the same study. This finding
led Ushijima to suggest that postsynaptic
cholinergic sensitivity to a direct cholinergic
agonist might be unaltered by chronic
haloperidol. However, it must be taken into
account that dopaminergic supersensitivity is
not yet fulIy developed after 24 hr of
withdrawal. The maximum effect is observed only
7 after the last injection of haloperidol (von
Voigtlander 1975). The process of REMSD produces
postsynaptic dopaminergic supersensitivity
(Tufik 1978; Arriaga 1988) and cholinergic
subsensitivity in the same way as chronic
haloperidol, but it seems that its maximal
effect develops earlier. This idea would explain
why REMSD inhibits the response induced either
by dopaminergic or cholinergie agonists, when
the tests are performed immediately after the
end of deprivation (Tufik 1987).
However, as the number of yawnings induced by
a direct cholinergic agonist (pilocarpine) had
returned to control levels after 24 hr, one
might suppose that the cholinergic system shows
a faster rcuperation, suggesting that it is
affected only indirectly by the REMSD process.
Furthermore, apomorphine-induced yawning was
still reduced after 24 hr, probably because the
presynaptic dopaminergic receptor was yet
subsensitive. The response to physostigmine was
intermediary, probably because the effects of
physostigmine, an anticholinesterase agonist
depend upon the availability of acetylcholine
released from presynaptic terminals. This
acetylcholine release is diminished due to the
dopaminergic postsynaptic supersensitivity.
In summary, the present data suggest that the
process does not occur simultaneously for both
systems and that it first takes place in the
system less affected by the procedure.
Accordingly we formulated the hypothesis that
REMSD acts initiallly on the dopaminergic
system, thus affecting the cholinergic system in
a secondary way.
