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Subline Differences In Behavioral Responses to Pharmacological Agents

Beatriz Moisset

Psychology Department
Temple University
Philadelphia, Pennsylvania

Mutations that modify the response to a drug or that cause some minor change in behavior are likely to remain unnoticed indefinitely. Thus, separate colonies that originated from an inbred strain may differ in many genes that could be detected only by using pharmacological or behavioral techniques.

The stimulant drug d-amphetamine causes a large increase in locomotor activity in C57BL/6J and C57BL/10J mice, but has only a moderate effect on C57BL/6By ( 1). Analysis of F1 and backcross matings suggests a one-gene model. A dominant mutation seems to have taken place in the C57BL/6By subline. A genetic difference in response to d-amphetamine may reflect a difference in norepinephrine receptor sensitivity and could be useful in studying the neurochemical regulation of locomotor activity.

There are large differences in the response to the narcotic effects of ethanol between inbred strains of mice. BALB/cJ mice have been repeatedly reported as sensitive to ethanol (long sleep time) ( 2, 3, 4). A mutation(s) appears to have occurred in BALB/cJ mice, changing from highly sensitive to resistant to ethanol. Sleep time after 4 g/kg of ethanol is 35.91 +/- 5.59 minutes as compared to previous reports that vary from 66 to 110 minutes. This possible mutation may have occurred quite recently and it is possible that BALB/cJ mice are still segregating for this gene. BALB/cBy mice, on the other hand, are very sensitive to ethanol. Their sleep time is 90.68 +/- 7.532 minute. This value resembles that of previous authors using BALB/cJ. This factor affecting the narcotic effects of ethanol has little or no effect on ethanol preference in a free choice between 10% ethanol and water. Both sublines of the BALB/c strain show a low preference, thus indicating a dissociation between these two physiological phenomena. A mutation has been reported that affects ethanol preference ( 5). C57BL/6A shows a lower preference than C57BL/6J. To our knowledge, no research has been done on whether these two sublines differ in ethanol sleep time.

Subline differences like the ones reported above may be useful in investigating one gene's effects in a fairly similar background. Pharmacogeneticists and behavioral geneticists may benefit from a search of mutations in sublines of inbred strains.


1. Moisset, B. (1977). Psychopharmacology 53: 263.
See also PubMed.

2. Damjanovich, R.P., and Mac Innes, J.W. (1973). Life Sci. 13: 55.

3. Belknap, J.K., Mac Innes, J.W., and MacClearn, G.E. (1972). Physiol. Behav. 9: 453.
See also PubMed.

4. Randall, C.L., and Lester, D. (1974). J. Pharm. Exp. Therap. 188: 27.
See also PubMed.

5. Poley, W. (1972). Behav. Genet. 2: 245.
See also PubMed.

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