ArticlesGenetic Determinants of Severity of Acute Withdrawal From Diazepam in Mice: Commonality With Ethanol and Pentobarbital
Section snippets
Subjects
Adult male mice (52–67-days-old at the time of testing) from 14 of the 15 inbred strains tested in our previous study (50) were used in this experiment. The following inbred strains were available in sufficient numbers for testing: 129/J, A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57BR/cdJ, C57L/J, CBA/J, DBA/1J, DBA/2J, PL/J, SJL/J, and SWR/J. Mice were purchased from the Jackson Laboratory, Bar Harbor, ME, and housed by strain, three to four animals per polycarbonate cage (28 × 17 × 11.5 cm)
Results
Results are shown in Fig. 1A and B. As we had seen previously, the inbred strains differed significantly in diazepam withdrawal severity (50). The time courses of withdrawal for four representative strains are depicted in Fig. 1A. The inbred strains are known to differ considerably in basal HIC severity 18, 50, and a significant main effect of strain on baseline HIC was detected, F(13, 140) = 31.05, p < 0.01; range of strain mean values: 0–4. As expected, treatment groups within strain did not
Discussion
The results of this study provide strong evidence that there are common genetic determinants of diazepam, ethanol, and pentobarbital withdrawal convulsions. There is substantial evidence to suggest that there should be a common neural mechanism underlying withdrawal from these three types of drugs. One receptor system known to mediate some of the effects of all three of these drugs is the GABA/benzodiazepine receptor/chloride ionophore complex (GRC). Besides distinct binding sites for GABA and
Acknowledgements
This study was supported by National Institute on Alcohol Abuse and Alcoholism Grants AA10760, AA06243, National Institute on Drug Abuse Grant DA05228, and a grant from the Department of Veterans Affairs. Pamela Metten was supported by National Institute on Drug Abuse Training Grant T32 DA 07262. We thank Sue Burkhart-Kasch for superb technical assistance, and Dr. Edward J. Gallaher for the drugs.
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