GENETIC VULNERABILITY TO DRUGS OF ABUSE

Project: Research project

Description

Individual differences in sensitivity to psychoactive drugs are determined
by many factors (eg, historical factors including drug history,
environmental factors such as social setting and learned associations, and
constitutional factors such as genetics). Among these, the notion that
genotype may predispose some individuals to extremes of drug sensitivity to
a number of compounds has gained much recent support. There is still little
information, however, regarding the extent to which genetic predisposition
to the effects of one class of drugs also predisposes to another class.
Similarly, we have only rudimentary knowledge about the genetic relatedness
of sensitivity, tolerance, and physical dependence. The proposed research will establish the genetic basis for sensitivities o
several behavioral effects (oral self-administration, acute thermal
response, behavioral activation and depression, loss of righting reflex,
and rotarod ataxia) of the agents diazepam, morphine, phenobarbital,
pentobarbital, and ethanol. Several doses of each compound will be tested
in twenty inbred strains of mice. Differences in sensitivity between
strains will be taken as evidence for genetic predisposition. Correlation
of mean train sensitivities will provide evidence for the generality of
genetic predisposition to these compounds. All strains will also be
rendered physically dependent upon each compound, and the severity of
withdrawal assessed. The genetic correlations between sensitivity and
withdrawal among he compounds will thus also be estimated. These results should provide rigorous, systematic evidence for or against e
hypothesis that genetic predisposition to a number of psychoactive drugs
which share some CNS depressant properties in common generalizes across
drugs of different pharmacological classes and may ultimately lead to a
better understanding of compulsive drug self-administration.
StatusFinished
Effective start/end date8/1/893/31/16

Funding

  • National Institutes of Health
  • National Institutes of Health: $322,145.00
  • National Institutes of Health: $163,725.00
  • National Institutes of Health: $383,125.00
  • National Institutes of Health: $372,008.00
  • National Institutes of Health: $283,500.00
  • National Institutes of Health: $331,261.00
  • National Institutes of Health: $272,160.00
  • National Institutes of Health: $226,741.00
  • National Institutes of Health: $394,671.00
  • National Institutes of Health: $331,767.00
  • National Institutes of Health: $339,750.00
  • National Institutes of Health
  • National Institutes of Health: $279,247.00
  • National Institutes of Health: $283,500.00
  • National Institutes of Health: $315,702.00
  • National Institutes of Health
  • National Institutes of Health: $334,884.00
  • National Institutes of Health: $361,173.00
  • National Institutes of Health
  • National Institutes of Health: $283,500.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

drug abuse
Street Drugs
quantitative trait loci
Quantitative Trait Loci
Self Administration
Hypnotics and Sedatives
Pharmaceutical Preparations
pentobarbital
Genetic Models
Genetic Predisposition to Disease
Ethanol
genes
Genes
Substance-Related Disorders
nitrous oxide
Pentobarbital
Central Nervous System Depressants
Diazepam
Righting Reflex
drugs

ASJC

  • Medicine(all)