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mise à jour du
6 novembre 2005
Life Science
1973; 11; 203-210
Yawning and stretching in rats induced
by intraventricularly administered zinc
Izumi K, Donaldson J, Barbeau A 
Department of Neurobiology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal 130, Quebec, Canada.


Administration of zinc into the left lateral ventricle of rats elicited yawning-stretching behavior. Yawning and stretching was not observed after injection of the metal ions manganese, copper and cadmium. Intraventricular injection of l-24-ACTH, synthetic n and B-LPH also evoked yawning and stretching after a latent period of 40-60 minutes. The administration of L-glutamate and D, L-glycine was ineffective in producing yawning-stretching behavior.
The observation that yawning and stretching crises of muscular hypertonus (which can be considered as an effect of the body to delay the onset of sleep or to reinforce wakefulness after sleep) are elicited by administration of adreno-corticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH) into the cerebrospinal fluid of mammals was first reported by Ferrari (1). Further studies from the same laboratory (2) revealed that this peculiar behavior was induced only through the administration of the component heptapeptide: methionine-glutamate-histidine-phenylalanine-arginine-tryptophan-glycirte (MetGlu-Hls-Phe-Arg-Try-Gly) common to both ACTH and MSH. The site of action of ACTH and/or MSH for these effects was thought to be in the hypothalamus and probably involved its connections with the descending and ascending reticular formation of the brain stem, usually considered responsible for yawning and stretching (2, 3). Yawning and stretching induced by ACTH was suppressed by chlorpromazine, atropine and diethazine, drugs known to act within the reticular formation (2).
During a previous study (4) concerned with the ability of certain metal ions to produce clonic-tonic seizures in rats it was observed that low doses of zinc, following injection into the left lateral ventricle, evoked a peculiar yawning-stretching syndrome in the treated animals. The present communication reports the results of experiments designed to elaborate further the role of zinc and other metal ions in the induction of the yawning-stretching phenomenon. In addition, the role of certain polypeptides in the initiation of this type of behavior was further expanded and confirmed.
The mechanism of action of zinc in the production of a yawning and stretching syndrome is not resolved by the present experiments. It would appear, however, that the behavioral response elicited by zinc is specific for this ion since copper and cadmium ions, both of which have similar physical and chemical properties to zinc (5), did not produce yawning and stretching in rats so treated. Manganese ions were similarly ineffective. Coupling of zinc with a particular amino acid may be a possibility (6), since both the content of ACTH and zinc have been found to increase in the serum under stress conditions (7). It is possible the "active" component of the metal-hormone coupling could be the zinc molecule. However amounts of zinc in MSH and B-LPH sufficient to cause the special behavior could not be detected, although large amounts of zinc in 24-ACTH were found. Additionally, the administration of L-glutamate and D,L-glycine, amino acids also known to bind zinc (8), did not cause yawning or stretching.
Another possibility to consider is that zinc is involved in the release of these peptides and that the special patterns of behavior were elicited as a result of the induced secretion of such hormone (s). This possibility can probably be ruled out since excessive grooming, yawning and stretching from zinc were similar in mode, but different in latency of onset and intensity from those induced by the peptides. Indeed, as previously stated, the latency of the induced patterns was much shorter with zinc and the intensity greater with the hormones.
An alternate possibility could be that zinc is involved in the mechanism of hormone-receptor interaction. Certain amino acids or peptides have a greater affinity for specific trace metals (6). On the other hand, it is known that the affinity of various trace metals for specific brain regions is not uniform and does not necessarily correspond with the regional concentration of a specific trace element (Donaldson et al., unpublished observation). For example, although the concentration of zinc is highest in the hippocampus and hypothalamus, the region with the highest affinity for exogenously administered zinc is the medulla oblongata (9). It is possible that a "functional" coupling between certain hormones and a trace metal exists and that the trace metal (here zinc) could serve to orient the hormonal structure towards specific, high affinity, regional receptor sites in the brain.
The results of our studies with a-NS}! and 8124-ACTH are in agreement with those of Ferrari and collaborators (1, 2). Because zinc has been known to increase and prolong the action of ACTH (10, 11, 12) and in view of our own results with intraventricular injections of zinc, the zinc content in these peptides was estimated and found to be negligible with the exception of 8124-ACTH which contained elevated amounts of the ion. Therefore, 8124-ACTH action in provoking yawning and stretching may not relate to its peptide structure but to its inherent zinc content. However, the fact that administration of 824-ACTH also caused this peculiar behavior with the same intensity and latency to that of MSH (a- and 8-), does indicate that the mechanism involved may be related to a structure common to all the peptides. Such a structure as postulated by Ferrari et al. (2) appears to be the amino acid sequence: Met-Glu-His-Phe-Arg-Try-Gly. Our studies thus repeat those of Ferrari et al. (2), and add further confirmation through the results obtained with 8-LPH (2,500 jig.), a fact previously unreported.
B-LPH has to be given in higher quantity for the same amount of the heptapeptide to have any potential effect, because of the differences in molecular weight between 8-MSH and 8-LPH. It is indeed probable that physiologically 8-LPH serves as a precursor to 8-MSH (13). It is noteworthy that the action of the polypeptides is of marked intensity, but of long latency; on the other hand that of zinc is of short latency, but of moderate intensity, therefore further studies on the exact mode of action will have to carried out.