A survey of acute and chronic heroin dependence in ten inbred mouse strains: evidence of genetic correlation with morphine dependence.
Heroin and morphine exposure can cause physical dependence, with symptoms manifesting during their withdrawal. Inter-individual differences in symptom frequency during morphine withdrawal are a common finding that, in rodents, is demonstrably attributable to genotype. However, it is not known whether inter-individual differences characterize heroin withdrawal, and whether such variation can be similarly influenced by genotype. Therefore, we injected mice of ten inbred strains with acute and chronic heroin doses and compared their jumping frequencies, a common index of withdrawal magnitude, during naloxone-precipitated withdrawal. The data revealed significant strain frequency differences (range after acute and chronic heroin injection: 0-104 and 0-142 jumps, respectively) and substantial heritability (h(2)=0.94 to 0.96), indicating that genetic variance is associated with heroin withdrawal. The rank order of strain sensitivity for acute and chronic heroin withdrawal jumping, and for the current heroin and previous morphine strain data, were significantly correlated (r=0.75-0.94), indicating their genetic and, ultimately, physiological commonality. These data suggest that the genetic liability to heroin dependence remains constant across a period of heroin intake, and that heroin and morphine dependence may benefit from common treatment strategies.
Klein
Gad
G
Neuropsychology Doctoral Subprogram, Queens College, City University of New York, Flushing, NY 11367, United States.
Juni
Aaron
A
Waxman
Amanda R
AR
Arout
Caroline A
CA
Inturrisi
Charles E
CE
Kest
Benjamin
B
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D014644:Genetic Variation; D005838:Genotype; D006556:Heroin Dependence / Q000235:genetics* / Q000523:psychology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000235:genetics* / Q000523:psychology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D009292:Narcotic Antagonists; D009270:Naloxone