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Bruce Nock, PhD
Current
Position
Associate Professor of Neurobiology in Psychiatry
Areas of Research Interests
Our animal studies and clinical findings indicate that chronic exposure to heroin or morphine causes modifications to the hypothalamic-pituitary-adrenocortical (HPA) axis that are opposite to those caused by stress and characteristic of those found in individuals at high risk for or suffering from posttraumatic stress disorder (PTSD). Our current research is concerned with the causes and consequences of the opiate-induced glucocorticoid deficit. We believe this is an important line of research for several reasons.
In particular, by decreasing the bioavailability of cortisol, the chief glucocorticoid in humans, opiates may provide relief from stress-related glucocorticoid overexposure which can be detrimental to both physical and mental health. This could be the biological basis for the long-held view that drug use is a self-medication against chronic stress.
Nevertheless, over the long run exposure to morphine overshoots the mark. Rather than merely counteracting the effects of stress and normalizing glucocorticoid levels, it leaves the individual in a state of glucocorticoid deficiency. This is likely to compromise the individuals ability to cope with, adapt to, and recover from everyday challenges and stressful events and conditions and may increase vulnerability to PTSD.
Finally, the glucocorticoid deficiency appears to contribute to the development of tolerance. Opiates remain the most effective therapy for persistent and moderate to severe pain, and morphine is the most commonly prescribed opiate. However, tolerance is a real problem. Clinically, it is manifested by an increase in the frequency of requests for medication. Unfortunately, this often is incorrectly interpreted as a sign of impending psychological dependence, i.e., addiction. This misunderstanding often leads to under-treatment; sometimes dosages are even lowered under these circumstances. If our hypothesis is correct, maintenance of normal levels of physiologically active glucocorticoid may be all that is required to block tolerance development and eliminate the need for progressively higher drug dosages, thereby, minimizing the physical and mental risks of morphine usage.
Key Publications
Nock B, Wich M, Cicero TJ: Chronic exposure to morphine increases corticosteroid-binding globulin. J Pharmacol Exp Ther 1997; 282:1262-1268.
Nock B, Cicero TJ, Wich M: Chronic exposure to morphine decreases physiologically active corticosterone in both male and female rats but by different mechanisms. J Pharmacol Exp Ther 1998; 286:875-882.
Nock, B, Wich, M, Cicero, TJ, OConnor, LH: Testosterone is required for corticosteroid-binding globulin upregulation by morphine to be fully manifested. Pharmacol Biochem Behav 2000; 67:193-198.