UNDERGRADUATE SUMMER RESEARCH PROGRAM
2010 NSSP Information
Ian A. Paul, Ph.D.
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Ian A. Paul, Ph.D. CPN Project Principal Investigator Professor Department of Psychiatry and Human Behavior The University of Mississippi Medical Center Jackson, Mississippi
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Key Laboratory Personnel:
Dorota Maciag, Ph.D., Post-DocLashondra Williams, Research Technician
David Coppinger, Graduate Student
Sharonda Swilley, Graduate Student
Kedra Wallace, Graduate Student
"Neurobehavioral Effects of Early Exposure to Psychotherapeutic Agents"
Dr. Paul's laboratory is currently pursuing two primary areas of research. Our research, funded by the CPN, is focused on the effects of early exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants on brain development and behavior. SSRIs are the pharmacotherapy of choice for pregnant and nursing mothers and recent studies have demonstrated that the fetus and nursing infant are exposed to drug concentrations similar to those of the mother. Little is known about the long-term neurobiological effects of early SSRI exposure however, recent studies indicate that such exposure may have lasting increases in irritability and impairment of fine motor behavior and pain sensitivity in humans. In rodent models of early antidepressant exposure, lasting impairment of male sexual behavior and aggressive response has been noted. We have recently demonstrated that the behavioral effects of early antidepressant exposure are also produced by highly selective SSRIs. Moreover, such exposure results in permanent reductions in the expression of tryptophan hydroxylase and the serotonin transporter which are critical proteins regulating serotonergic circuits (Maciag et al., Neuropsychopharmacology, 2005).
Since our initial observation that nitric oxide synthase (NOS) inhibitors have antidepressant‑like actions (see Harkin et al., 1999 and Karolewicz et al., 1999), we have continued to examine the functional significance of this signaling system in the actions of antidepressants and the pathophysiology of depression. To this end, we are studying the antidepressant-like effects of selective inhibitors of NOS by employing more sophisticated analysis of the forced swim test using the methods of Detke et al., and by examining the effect of repeated social defeat on NOS activity and expression in the CNS. In addition, we are conducting studies using chemical lesion of monoaminergic neurotransmitter systems to examine the interaction of monoaminergic neurotransmitter regulation with nitric oxide signaling systems.
Further, we have begun projects examining the role of nitric oxide signaling in antidepressant-responsive behaviors in acute (forced swim and tail suspension tests) and chronic (social defeat, learned helplessness) paradigms using mice with selective knock-out of neuronal and endothelial NOS. The laboratory also maintains an interest in the effect of social interactions on behavior in antidepressant-sensitive behavioral paradigms such as the forced swim test (Karolewicz, B. and Paul, I.A., Eur. J. Pharmacol. 415:197-201, 2001.).