Selection for pentobarbital withdrawal severity: correlated differences in withdrawal from other sedative drugs.
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.
Kliethermes
Christopher L
CL
Department of Behavioral Neuroscience, Oregon Health & Science University and the Portland Alcohol Research Center, Veterans Affairs Medical Center, c/o Portland VA Medical Center, Portland, OR 97239, USA. kliether@ohsu.edu
Metten
Pamela
P
Belknap
John K
JK
Buck
Kari J
KJ
Crabbe
John C
JC
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000009:adverse effects; D003975:Diazepam / Q000009:adverse effects; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010424:Pentobarbital / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D012641:Selection, Genetic; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000235:genetics*; D013997:Time Factors; D000077334:Zolpidem
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D000431:Ethanol; D000077334:Zolpidem; D010424:Pentobarbital; D003975:Diazepam