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.

Current members of the Schulteis Laboratory include (l-r): Lab Manager Clay Archer, Graduate Student David Chiang, Student Research Assistants Diep Ho and Priyanka Soni, Graduate Student Monica Wolfe, Senior Fellow Zhongqi (David) Zhang, MD, and PI Gery Schulteis, PhD. Not pictured: Student Research Assistants Susanne Chang and Ray Scott.

Selected Publications

Criner, S., Liu, J., & Schulteis, G. (2007). Rapid neuroadaptation in the nucleus accumbens and bed nucleus of the stria terminalis mediates suppression of operant responding during withdrawal from acute opioid dependence. Neuroscience, 144, 1436-1446.

Zhang, Z., & Schulteis, G. (2008). Withdrawal from acute morphine dependence is accompanied by increased anxiety-like behavior in the elevated plus maze. Pharmacology Biochemistry and Behavior, 89, 392-403.

Schulteis, G. Archer, C., Tapert, S. F., & Frank, L. R. (2008). Intermittent binge alcohol exposure during the periadolescent period induces spatial working memory deficits in young adult rats. Alcohol, in press.

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.

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., 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.

Complete PubMed publication list here.