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Effect of cadmium on ethanol induced sleeping time in mice
Pergamon Press
Life Sciences, Vol. 28, pp. 2917-2923
Printed in the U.S.A.
EFFECT
OF CADMIUM
Hiro-aki Institute
ON ETHANOL
Yamamoto,
INDUCED
Den'etsu
of Community Niihari,
SLEEPING
TIME IN MICE
Sutoo and Shogo Misawa
Medicine, University Ibaraki 305, Japan
of Tsukuba
(Received in final form April 20, 1981)
Summary The effect of cadmium on sleeping time induced by ethanol was studied in mice. When 0.25, 2.5 or 5.0
mg/kg of CdCl, was injected intraperitoneally (i.p.), the ethanol induced sleeping time was enhanced by 50 %, 100 % or 150 % from that of saline treated mice. The enhancement of ethanol induced sleeping time by cadmium was completely blocked by intracerebroventricular (i.vt.) pretreatment with CDTA, an agent that chelates This indicates that the ethanol induced cadmium ion. sleeping time was enhanced by a part of cadmium which passed through blood brain barrier after the i.p. injection. On the other hand, the ethanol induced sleeping time was also increased by 50 % with i.vt. injection of L-serotonin but not altered with L-dopamine or Lnorepinephrine. In addition to this, i.vt. injection of L-serotonin plus L-norepinephrine enhanced by 170 % the ethanol induced sleeping time. Furthermore, the enhancement of ethanol induced sleeping time by cadmium was potentiated by i.vt. treatment of L-serotonin or L-norepinephrine but not by L-dopamine. These results suggest that the enhancement of ethanol induced sleeping time by cadmium may be caused by an increase in L-serotonin levels or both L-serotonin and L-norepinephrine levels but not by L-dopamine levels in brain of mouse. Intravenous injection of L-serotonin or L-norepinephrine has been shown to produce slow wave sleep in birds (l-3) and many reports have suggested that sleep might be produced by both L-serotonin and L-norepinephrine in mammal (4-7). However, Tabakoff and Boggan (8) reported that L-serotonin levels of mouse brain were unaffected by injection of ethanol. In the brain of acutely ethanol intoxicated animals, no obvious changes were found in the content (9,10), and metabolism of L-serotonin (11). Similarly the metabolism of L-serotonin by brain tissue in vitro was also unaffected by an anesthetic dose of ethanol (12). -The results suggest that sleep induced by ethanol was not produced by an increase of L-serotonin or L-norepinephrine levels in brain. However, many reports showed that the ethanol induced sleeping time of mice treated with a monoamine oxidase inhibitor, which increase L-serotonin, L-norepinephrine and L-dopamine levels in brain, was enhanced more than 100 %. This finding 0024-3205/81/262917-07$02.00/O Copyright (c) 1981 Pergamon Press Ltd.
Life Sciences, Vol. 28, pp. 2917-2923
Printed in the U.S.A.
EFFECT
OF CADMIUM
Hiro-aki Institute
ON ETHANOL
Yamamoto,
INDUCED
Den'etsu
of Community Niihari,
SLEEPING
TIME IN MICE
Sutoo and Shogo Misawa
Medicine, University Ibaraki 305, Japan
of Tsukuba
(Received in final form April 20, 1981)
Summary The effect of cadmium on sleeping time induced by ethanol was studied in mice. When 0.25, 2.5 or 5.0
mg/kg of CdCl, was injected intraperitoneally (i.p.), the ethanol induced sleeping time was enhanced by 50 %, 100 % or 150 % from that of saline treated mice. The enhancement of ethanol induced sleeping time by cadmium was completely blocked by intracerebroventricular (i.vt.) pretreatment with CDTA, an agent that chelates This indicates that the ethanol induced cadmium ion. sleeping time was enhanced by a part of cadmium which passed through blood brain barrier after the i.p. injection. On the other hand, the ethanol induced sleeping time was also increased by 50 % with i.vt. injection of L-serotonin but not altered with L-dopamine or Lnorepinephrine. In addition to this, i.vt. injection of L-serotonin plus L-norepinephrine enhanced by 170 % the ethanol induced sleeping time. Furthermore, the enhancement of ethanol induced sleeping time by cadmium was potentiated by i.vt. treatment of L-serotonin or L-norepinephrine but not by L-dopamine. These results suggest that the enhancement of ethanol induced sleeping time by cadmium may be caused by an increase in L-serotonin levels or both L-serotonin and L-norepinephrine levels but not by L-dopamine levels in brain of mouse. Intravenous injection of L-serotonin or L-norepinephrine has been shown to produce slow wave sleep in birds (l-3) and many reports have suggested that sleep might be produced by both L-serotonin and L-norepinephrine in mammal (4-7). However, Tabakoff and Boggan (8) reported that L-serotonin levels of mouse brain were unaffected by injection of ethanol. In the brain of acutely ethanol intoxicated animals, no obvious changes were found in the content (9,10), and metabolism of L-serotonin (11). Similarly the metabolism of L-serotonin by brain tissue in vitro was also unaffected by an anesthetic dose of ethanol (12). -The results suggest that sleep induced by ethanol was not produced by an increase of L-serotonin or L-norepinephrine levels in brain. However, many reports showed that the ethanol induced sleeping time of mice treated with a monoamine oxidase inhibitor, which increase L-serotonin, L-norepinephrine and L-dopamine levels in brain, was enhanced more than 100 %. This finding 0024-3205/81/262917-07$02.00/O Copyright (c) 1981 Pergamon Press Ltd.