Gerard Schulteis, Ph.D.

Important elements in the use of opiate analgesics are tolerance, dependence and withdrawal.   A crucial question relates to the neuroanatomical circuits mediating dependence and abstinence.  This group’s research demonstrated that affective or “emotional” signs of opioid withdrawal such as dysphoria and anxiety-like behavior are evoked following acute or occasional intermittent morphine treatment.  These findings suggest that neural circuits mediating reward and affect may be sensitive to rapid opioid neuroadaptation.  Recently, this group identified limbic and basal forebrain reward circuitry (e.g. amygdala, nucleus accumbens, bed nucleus of the stria terminalis) that mediate affective components of opioid withdrawal.  Opioids in these limbic and basal forebrain nuclei produce analgesia, and these regions interact directly with well-defined supraspinal pain modulatory circuitry. It is hypothesized that neuroadaptation within these brain regions is responsible for affective signs of acute opioid withdrawal, and may also contribute to withdrawal-associated hyperalgesic states. An ultimate goal is to understand biological mediators of vulnerability to opioid dependence and addiction, with the working hypothesis that individual variability in the expression of withdrawal signs following an initial exposure to opioids might be one factor that imparts increased vulnerability.  Thus, acute opioid dependence may have special relevance to the switch from initial use of an opioid to compulsive use.  Finally, the work is relevant to understanding how affect and mood influence perception of pain, and conversely how pain states influence/affect mood (e.g. depression in chronic pain patients). The trainees would explore the relationship between these supraspinal systems mediating affective withdrawal and hyperalgesic states to delineate functional pathways linking structures participating in the expression of individual signs of withdrawal.

Selected Publications
Schulteis G, Liu J. Brain reward deficits accompany withdrawal (hangover) from acute ethanol in rats  Alcohol 39:21-28, 2006.

Schulteis G, Liu J, Amital N, Tzeng S. Context- and cue-conditioned potentiation of acute morphine dependence and withdrawal. Pharmacol Biochem Behav 82:82-89, 2005.

Schulteis, G.,  Morse, A. C., & Liu, J.  Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence. Psychopharmacology, 175, 463-472, 2004.

Liu, J., & Schulteis, G. Brain reward deficits accompany naloxone-precipitated withdrawal from acute opioid dependence. Pharmacology Biochemistry and Behavior, 79, 101-108. 2004.

Azar, M. R., Jones, B. C., & Schulteis, G  Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal. Psychopharmacology, 170, 42-50, 2003.

Schulteis, G.,  Morse, A. C., & Liu, J. Repeated experience with naloxone facilitates acute morphine withdrawal: Potential role for conditioning processes in acute opioid dependence  Pharmacology Biochemistry and Behavior, 76, 493-503, 2003.

Schulteis, G., Ahmed, S., Morse, A. C. Koob, G. F., & Everitt, B. J.. Lesions of the basolateral nucleus of the amygdala abolish conditioned opiate withdrawal. Nature, 405, 1013-1014, 2000.