Annotation Local Anesthetics and Mouse Brain Dopamine
T. W. GAGE and R. L. DORRIS
Department of Pharmacology, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, Texas 75246, USA J Dent Res 56(12): 1492, December 1977. Many studies show that drugs which lower brain monoamine concentrations also lower the convulsive threshold (AZZARO ET AL., J Pharmacol Exp Ther 180:558, 1972; GRAY and RAUH, J Pharmacol Exp Ther 177:206-218, 1971). This would suggest that normally brain aminergic systems are important in countering convulsions and may possibly be activated during convulsive episodes. The lowering of midbrain dopamine in mice after lidocaine, reported by CIAR LONE and SMUDSKI (JDent Res 55-465, 1976) would be in agreement with this supposition. It would seem that additional studies regarding possible effects of local anesthetics on brain amines might provide information that is useful in the understanding of mechanisms involved in various convulsive disorders. We compared the effects of lidocaine and tetracaine on levels of dopamine in mouse brain and found the action of tetracaine to be different from that of lidocaine. Female TEX: (ICR) mice (average 26 gins) were injected intraperitoneally with 0.1 ml/10 gm body weight of a water solution of either lidocaine* or tetracaine and killed at designated times (table) by chloroform asphyxiation. Brains were divided according to GLOWINSKI and IVERSEN (J Neurochem 13: 655-669, 1966) into 3 parts - telencephalon (forebrain), mesencephalon-diencephalon (midbrain), and metencephalon-myelencephalon (hindbrain). Received for publication July 11, 1977. Accepted for publication September 12, 1977. *Lidocaine (Xylocaine HCI) furnished by Astra Pharm. Prod. Inc.
Tissues from 2 mice were pooled (except when whole brain dopamine was determined) and dopamine estimated according to NEFF and COSTA (Life Sci 5:951, 1966). Because hindbrain levels of dopamine were almost beyond detection, data on the hindbrain are not included. The results (table) indicate that lidocaine had no significant effect on dopamine levels in either forebrain or hindbrain. But, tetracaine significantly elevated dopamine levels in forebrain and midbrain and the effect was clearly observable when whole brain dopamine was measured. It is difficult to understand why we could not replicate the findings of Ciarlone and Smudski. In a second series of animals, we gave doses of lidocaine as high as 100 mg/kg and waited for up to 15 minutes before killing the animals. Again no detectable depletion of mouse brain dopamine was seen. Perhaps a mouse strain or sex difference accounts for this incon-
sistency. Tetracaine elevated brain dopamine, whereas lidocaine did not. Since both drugs in the doses used produced convulsions, this indicates that convulsions per se were not causally related to the change in brain dopamine levels after tetracaine. Further, in preliminary studies, we found that if tetracaine-induced convulsions were blocked by prior treatment of mice with diazepam, dopamine levels were still elevated. Further experiments are in progress in an attempt to learn something of the mechanism involved in the tetracaine effects.
TABLE EFFECT OF LOCAL ANESTHETICS ON
MOUSE BRAIN DOPAMINE LEVELS Dopamine(yg/gm + SEM) Lidocaine Forebrain Midbrain Whole brain
Tetracaine
Control
Treated
Control
Treated
2.32 + 0.13 0.47 + 0.02
2.51 + 0.10* 0.48 + 0.05*
2.77 ± 0.14 0.45 + 0.06 1.01 + 0.05
3.46 + 0 03t 0. 74 + 0.08 t 1.55 + 0.13O
-
Mice uere given lidocaine (65 mg/kg) or tetracaine (50 mg/kg) intraperitoneally and killed 7 minutes later (15 minutes later in case of whole brain experiments).
'Not significantly different from control. t P
< 0.0025. 3 P < 0.025. § P < 0.005.
1492 Downloaded from jdr.sagepub.com at Bobst Library, New York University on April 21, 2015 For personal use only. No other uses without permission.
T. W. GAGE and R. L. DORRIS
Department of Pharmacology, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, Texas 75246, USA J Dent Res 56(12): 1492, December 1977. Many studies show that drugs which lower brain monoamine concentrations also lower the convulsive threshold (AZZARO ET AL., J Pharmacol Exp Ther 180:558, 1972; GRAY and RAUH, J Pharmacol Exp Ther 177:206-218, 1971). This would suggest that normally brain aminergic systems are important in countering convulsions and may possibly be activated during convulsive episodes. The lowering of midbrain dopamine in mice after lidocaine, reported by CIAR LONE and SMUDSKI (JDent Res 55-465, 1976) would be in agreement with this supposition. It would seem that additional studies regarding possible effects of local anesthetics on brain amines might provide information that is useful in the understanding of mechanisms involved in various convulsive disorders. We compared the effects of lidocaine and tetracaine on levels of dopamine in mouse brain and found the action of tetracaine to be different from that of lidocaine. Female TEX: (ICR) mice (average 26 gins) were injected intraperitoneally with 0.1 ml/10 gm body weight of a water solution of either lidocaine* or tetracaine and killed at designated times (table) by chloroform asphyxiation. Brains were divided according to GLOWINSKI and IVERSEN (J Neurochem 13: 655-669, 1966) into 3 parts - telencephalon (forebrain), mesencephalon-diencephalon (midbrain), and metencephalon-myelencephalon (hindbrain). Received for publication July 11, 1977. Accepted for publication September 12, 1977. *Lidocaine (Xylocaine HCI) furnished by Astra Pharm. Prod. Inc.
Tissues from 2 mice were pooled (except when whole brain dopamine was determined) and dopamine estimated according to NEFF and COSTA (Life Sci 5:951, 1966). Because hindbrain levels of dopamine were almost beyond detection, data on the hindbrain are not included. The results (table) indicate that lidocaine had no significant effect on dopamine levels in either forebrain or hindbrain. But, tetracaine significantly elevated dopamine levels in forebrain and midbrain and the effect was clearly observable when whole brain dopamine was measured. It is difficult to understand why we could not replicate the findings of Ciarlone and Smudski. In a second series of animals, we gave doses of lidocaine as high as 100 mg/kg and waited for up to 15 minutes before killing the animals. Again no detectable depletion of mouse brain dopamine was seen. Perhaps a mouse strain or sex difference accounts for this incon-
sistency. Tetracaine elevated brain dopamine, whereas lidocaine did not. Since both drugs in the doses used produced convulsions, this indicates that convulsions per se were not causally related to the change in brain dopamine levels after tetracaine. Further, in preliminary studies, we found that if tetracaine-induced convulsions were blocked by prior treatment of mice with diazepam, dopamine levels were still elevated. Further experiments are in progress in an attempt to learn something of the mechanism involved in the tetracaine effects.
TABLE EFFECT OF LOCAL ANESTHETICS ON
MOUSE BRAIN DOPAMINE LEVELS Dopamine(yg/gm + SEM) Lidocaine Forebrain Midbrain Whole brain
Tetracaine
Control
Treated
Control
Treated
2.32 + 0.13 0.47 + 0.02
2.51 + 0.10* 0.48 + 0.05*
2.77 ± 0.14 0.45 + 0.06 1.01 + 0.05
3.46 + 0 03t 0. 74 + 0.08 t 1.55 + 0.13O
-
Mice uere given lidocaine (65 mg/kg) or tetracaine (50 mg/kg) intraperitoneally and killed 7 minutes later (15 minutes later in case of whole brain experiments).
'Not significantly different from control. t P
< 0.0025. 3 P < 0.025. § P < 0.005.
1492 Downloaded from jdr.sagepub.com at Bobst Library, New York University on April 21, 2015 For personal use only. No other uses without permission.
