Strain differences in adrenalectomy-induced alterations in nicotine sensitivity in the mouse.

Adult mice of four inbred strains (A, BUB, C57BL, DBA) and two selectively bred lines [Long-Sleep (LS) and Short-Sleep (SS)] were tested for differences in glucocorticoid regulation of nicotine sensitivity. One week following adrenalectomy (ADX), animals were tested for nicotine sensitivity in a battery of tests that included acoustic startle response, Y-maze activity (line crosses and rearings), heart rate and body temperature. Although each type of animal tested had increased nicotine sensitivity in at least one of the test battery measurements, there was clear evidence for a genetic influence on the scope of ADX-induced changes in sensitivity. LS animals had the largest increase in sensitivity with altered responses in four of five tests following ADX. The sensitivity of DBA animals was increased in two tests while for A, BUB, C57BL and SS animals, only one test was affected. ADX-induced alterations in nicotine sensitivity could not be explained on the basis of changes in nicotinic receptor number since changes were consistent across strains. The mechanism by which ADX causes increased nicotine sensitivity is not known. However, these data support the hypothesis that nicotine sensitivity is modulated by adrenal glucocorticoid secretion and also suggest that this phenomenon is under strict genetic control.