mise à jour du
29 août 2002
Arch. int. Pharmacodyn 1990; 308; 32-38
 Modifications on dopaminergic and cholinergic systems induced by the water tank technique: analysis through yawning behavior
BG Neuman, LR Trocone, S Braz, S Tufik
department of psychobiology, Escola Paulista de Medicina,PO box 20399, CEP 04034 Sao Paulo, Brasil
Phylogenetic data bearing on the REM sleep learning connection JM Siegel
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.

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