Susan L. Ingram, PhD
Assistant Professor

Research Interests:

Neural Mechanisms of Morphine Tolerance and Dependence

Chronic morphine administration induces adaptations in neurons resulting in opioid tolerance and dependence. The periaqueductal gray area (PAG) neurons are an integral part of the descending pathway that modulates pain impulses in the spinal cord and these neurons are implicated in the expression of many behavioral signs of opioid withdrawal. However, the cellular mechanisms underlying the changes observed after chronic opioid administration are not understood. My laboratory uses whole-cell patch-clamp recordings from brain-slices of the PAG to study the cellular mechanisms of opiate tolerance and dependence. We have previously found that chronic morphine treatment changes the efficacy of coupling of µ-opioid receptors to their effectors resulting in an increased release of GABA from PAG neurons. We are interested in further exploring these changes within the context of the involvement of PAG neurons in the descending pain pathway and their resulting effects on pain modulation. We are collaborating with the laboratory of Dr. Michael Morgan so that we might correlate cellular changes in the PAG with behavioral measures of pain and tolerance to morphine.

Regulation of Synaptic Transmission in the Midbrain by the Dopamine Transporter

The laboratory is also interested in the cellular mechanisms associated with other drugs of abuse such as psychostimulants (cocaine and amphetamines). The main cellular target for cocaine and amphetamine are the monoamine neurotransmitter transporters. These transporters are also the targets for therapeutic drugs for disorders such as depression and attention deficit disorder. Although the transporters are primarily known for regulating the extracellular concentrations of neurotransmitters through reuptake of released neurotransmitters, they have significant electrical activities as well. Our recent studies of the electrical properties of the monoamine transporters have shown that these transporters have a potential role in modulating excitability of midbrain neurons (see recent publications). Future studies are planned to determine the relevance of transporter-associated currents in the regulation of synaptic transmission in monoaminergic neurons associated with reward pathways within the midbrain.

Recent Publications:

Ingram, S.L. , Prasad, B.M. and Amara, S.G. (2002) Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons. Nature Neuroscience 5:971-8.

Ingram, S.L. (2000) Cellular and molecular mechanisms of opioid action, Progress in Brain Research: Nervous System Plasticity and Chronic Pain 129:483-492.

Christie, M.J., Connor, M., Vaughan, C.W., Ingram, S.L., Bagley, E.E. (2000). Cellular actions of opioids and other analgesics: implications for synergism in pain relief. Clinical & Experimental Pharmacology & Physiology, 27:520-3.

Ingram, S.L. and Amara, S.G. (2000). Arachidonic acid stimulates a novel cocaine-sensitive cation conductance associated with the human dopamine transporter, Journal of Neuroscience 20(2):550-557.

Christie, M.J., Vaughan, C.W., and Ingram, S.L. (1999). Opioids, NSAIDS and 5-lipoxygenase inhibitors act synergistically in brain via arachidonic acid metabolism. Inflammation Research 48(1): 1-4.

Ingram, S.L., Vaughan, C.W., Bagley, E., Connor, M., and Christie, M.J. (1998). Enhanced opioid efficacy in opioid dependence is due to an altered signal transduction pathway. Journal of Neuroscience 8(24): 10269-76.

Connor, M., Ingram, S.L. and Christie, M.J. (1997). Cortistatin increase of a potassium conductance in rat locus coeruleus neurons. British Journal of Pharmacology 122:1567-1572.

Vaughan, C.W., Ingram, S.L., Connor, M. and Christie, M.J. (1997). How opioids inhibit GABA-mediated neurotransmission. Nature 390: 611-614.

Ingram, S., Wilding, T.J., McCleskey, E.W. and Williams, J.T. (1997). Efficacy and kinetics of opioid action on acutely dissociated neurons. Molecular Pharmacology 52:136-143.

Current Grant Support:

Morgan, M. M. & Ingram, S. L. (co-P.I) National Institute on Drug Abuse. Cellular mechanisms of opioid tolerance. (RO1 DA015498). May, 2003 to April, 2008. $900,000 direct costs.

Ingram, S. L. National Alliance of Research on Schizophrenia and Depression (NARSAD). Regulation of synaptic transmission in the midbrain by the dopamine transporter. July, 2003-June, 2005. $60,000.