GENETIC DIFFERENCES IN STRESS-INDUCED ANALGESIA: COVARIATION WITH AVOIDANCE LEARNING

CAROLYN SACHIKO NAGASE, Purdue University

Abstract

This dissertation presents eight experiments examining stress-induced analgesia (SIA) in animals selectively bred for either good or poor avoidance learning. Animals of the high avoidance (SHA) and low avoidance (SLA) lines differ markedly in avoidance learning and in emotional reactivity. Another correlate of the avoidance phenotypes is a reliable difference in SIA which is presented here. Throughout this series of experiments, exposure to electric tail-shock produced a profound SIA in SLA animals, whereas the SIA was modest in SHA animals. Experiments 1, 2, and 3 demonstrated that opiate antagonists are ineffective in attenuating the SIA of either line. Experiment 4 showed that animals of both lines are responsive to the analgesic effects of Morphine, and that these effects are blockable by Naltrexone. Thus, the SIAs are probably mediated by non-opioid mechanisms. Because SLA animals have larger adrenal glands than SHA animals, Experiment 5 examined whether this morphological difference contributes to the observed difference in SIA. Bilateral adrenalectomy did not affect the SIA of either line, which provides further evidence that these SIAs are mediated by neither endogenous opiates, nor cortiosterone, nor medullary hormones. Experiment 6 and Experiment 7 addressed whether the serotonergic system contributed to SIA. Fluoxetine Hydrochloride, a specific re-uptake inhibitor of serotonin did not attenuate the SIA of either line, which suggests that these SIAs are not dependent on serotonin. In Experiment 8, pretreatment with Reserpine, which depletes central and peripheral monoamines, partially attenuated SIA, and in combination with stress, was lethal for some SLA animals, whereas neither of these effects were observed in SHA animals. The overall results are discussed in terms of newly identified genetic differences in drug sensitivity and non-opioid SIA which co-vary with the avoidance phenotypes, and the possible mediation of these SIAs by the adrenergic system.

Degree

Ph.D.

Subject Area

Psychobiology

COinS