ISSN:
1432-1912
Keywords:
Diazepam
;
Chlorpromazine
;
Benzoctamine
;
Spinal Cord
;
GABA
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The effect of diazepam on several activities of the spinal cord was investigated in decerebrate and high-spinal cats by recording neurograms from lumbosacral ventral and dorsal roots and by measuring the levels of γ-aminobutyric acid (GABA) in the lumbosacral spinal cord. Chlorpromazine and benzoctamine were included for comparison with diazepam in part of the investigation. Diazepam depressed but did not abolish monosynaptic and polysynaptic ventral root reflex (VRR) responses; it was 3 to 5 times more potent in the decerebrate than in the spinal cat. Spontaneous gamma fibre activity was markedly and almost equally reduced by diazepam in both preparations. Dorsal root potentials (DRP's) and the presynaptic inhibition of monosynaptic VRR's elicited by stimulation of peripheral afferents were enhanced and prolonged by diazepam to the same extent in spinal and decerebrate animals; however, the enhancement of DRP's elicited by stimulation of the medullary reticular formation required approximately 3 time higher doses of diazepam. The effect of diazepam on presynaptic inhibition and DRP's was antagonized by bicuculline in a surmountalbe manner. Following amino-oxy-acetic acid (AOAA), which more than doubled the levels of endogenous GABA in the spinal cord, presynaptic inhibition and DRP's were enhanced but the amplitude of monosynaptic VRR responses was unaffected; diazepam further enhanced presynaptic inhibition and DRP's but no longer depressed monosynaptic VRR responses. Thiosemicarbazide, which decreased the level of GABA in the spinal cord by about 60%, reduced presynaptic inhibition and DRP's and prevented the augmenting effect of diazepam on these parameters. Doses of the organic solvent of diazepam in the 10 times higher amounts than used in the experiments with diazepam had only negligible and short-lasting effects; it seems very unlikely that the solvent contributed appreciably to the effect of diazepam solutions. It is concluded that 1) diazepam affects various activities of the spinal cord predominantly by a spinal site of action, 2) normal levels of GABA in the spinal cord seem to be a prequisite for the augmenting effect of diazepam on presynaptic inhibition in the spinal cord, 3) diazepam may act by altering the metabolism or disposition of GABA. Whether the enhancement of presynaptic inhibition fully accounts for the depressant effect of diazepam on monosynaptic and polysynaptic VRR's and on the gamma activity cannot be decided yet. In contrast to diazepam, chlorpromazine and benzoctamine did not enhance DRP's. Chlorpromazine depressed monosynaptic and polysynaptic VRR's and gamma activity only in the decerebrate cat. Benzoctamine was approximately as potent as diazepam in depressing monosynaptic and polysynaptic VRR responses in both preparations and in reducing gamma fibre activity in decerebrate cats, but was less potent than diazepam on the gamma fibre activity in spinal animals.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00504702
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