TY - JOUR
T1 - Selection for pentobarbital withdrawal severity
T2 - Correlated differences in withdrawal from other sedative drugs
AU - Kliethermes, Christopher L.
AU - Metten, Pamela
AU - Belknap, John K.
AU - Buck, Kari J.
AU - Crabbe, John C.
N1 - Funding Information:
The authors would like to thank Cathy Merrill and Charlotte Wenger for expert technical assistance. This research was supported by NIH grants AA10760, AA05828, AD05228, and AD06243, and by the Department of Veterans Affairs.
PY - 2004/5/29
Y1 - 2004/5/29
N2 - In mice, withdrawal from agents that depress central nervous system function, such as barbiturates and benzodiazepines, results in the production of a withdrawal syndrome, one feature of which is increased severity of handling induced convulsions (HICs). High and Low Pentobarbital Withdrawal mice (HPW and LPW) were selectively bred to display severe and mild pentobarbital withdrawal HICs, respectively. These mice provide a valuable means to assess genetic correlations between withdrawal from pentobarbital and other sedative agents. We tested HPW and LPW mice for severity of HICs elicited during withdrawal from ethanol, diazepam, and zolpidem, and measured consumption of and preference for pentobarbital solutions in HPW and LPW mice. HPW mice displayed greater HICs than LPW mice during ethanol and zolpidem withdrawal, but differed less robustly during diazepam withdrawal. LPW mice consumed more pentobarbital in a solution of a moderate concentration than did HPW mice, but did not consume more pentobarbital at a higher or lower concentration. These results indicate that some of the same genes that affect the severity of withdrawal from pentobarbital also influence ethanol and zolpidem withdrawal, but that diazepam withdrawal may be less influenced by these genes.
AB - In mice, withdrawal from agents that depress central nervous system function, such as barbiturates and benzodiazepines, results in the production of a withdrawal syndrome, one feature of which is increased severity of handling induced convulsions (HICs). High and Low Pentobarbital Withdrawal mice (HPW and LPW) were selectively bred to display severe and mild pentobarbital withdrawal HICs, respectively. These mice provide a valuable means to assess genetic correlations between withdrawal from pentobarbital and other sedative agents. We tested HPW and LPW mice for severity of HICs elicited during withdrawal from ethanol, diazepam, and zolpidem, and measured consumption of and preference for pentobarbital solutions in HPW and LPW mice. HPW mice displayed greater HICs than LPW mice during ethanol and zolpidem withdrawal, but differed less robustly during diazepam withdrawal. LPW mice consumed more pentobarbital in a solution of a moderate concentration than did HPW mice, but did not consume more pentobarbital at a higher or lower concentration. These results indicate that some of the same genes that affect the severity of withdrawal from pentobarbital also influence ethanol and zolpidem withdrawal, but that diazepam withdrawal may be less influenced by these genes.
KW - Barbiturate
KW - Benzodiazepine
KW - Drugs of abuse: alcohol, barbiturates, and benzodiazepines
KW - Genetics
KW - Neural basis of behavior
KW - Pentobarbital withdrawal
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U2 - 10.1016/j.brainres.2004.02.040
DO - 10.1016/j.brainres.2004.02.040
M3 - Article
C2 - 15120579
AN - SCOPUS:2142821387
SN - 0006-8993
VL - 1009
SP - 17
EP - 25
JO - Brain research
JF - Brain research
IS - 1-2
ER -