Our research focuses on molecular and biochemical mechanisms in neuropharmacology with a special interest in characterizing drug effects at the level of receptors and second messenger systems. Two classes of drugs of abuse, opioids and cannabinoids, bind to receptors which act through specific G-proteins to inhibit adenyl cyclase. This laboratory characterizes these reactions by exploring components in the pathway, including the receptor, the inhibitory G-proteins, the adenyl cyclase catalytic unit, and the inhibition of protein phosphorylation. This research examines the effect of chronic opioid and the treatment of signal transduction to understand how tolerance may be produced by changes in receptor coupling to effectors. Another major research goal in the laboratory is purification of endogenous cannabinoid substances from brain. A final research interest involves mechanisms of cocaine action to define the structural aspects of the cocaine pharmacophore. The procedures used in our laboratory include receptor binding techniques, assay of G-proteins and cyclic nucleotides, protein phosphorylation, and mRNA analysis.
Martin TJ, Buechler NL, Kim SA, Ewan EE, Xiao R, Childers SR. Involvement of the lateral amygdala in the antiallodynic and reinforcing effects of heroin in rats after peripheral nerve injury. Anesthesiology. 2011; 114(3):633-642.
Oleson EB, Talluri S, Childers SR, Smith JE, Roberts DCS, Bonin KD, Budygin EA. Dopamine uptake changes associated with cocaine self-administration. Neuropsychopharmacology. 2009; 34(5):1174-1184.
Manning JR, Sexton T, Childers SR, Davies HML. 1-Naphthyl and 4-indolyl arylalkylamines as selective monoamine reuptake inhibitors. Bioorg Med Chem Lett. 2009; 19(1):58-61.
Murthy V, Martin TJ, Kim S, Davies HML, Childers SR. In vivo characterization of a novel phenylisothiocyanate tropane analog at monoamine transporters in rat brain. J Pharmacol Exp Ther. 2008; 326(2):587-595.
Clayton BA, Hayashida K-i, Childers SR, Xiao R, Eisenach JC. Oral donepezil reduces hypersensitivity after nerve injury by a spinal muscarinic receptor mechanism. Anesthesiology. 2007; 106(5):1019-1025.
Murthy V, Davies HML, Hedley SJ, Childers SR. Irreversible binding of a novel phenylisothiocyanate tropane analog to monoamine transporters in rat brain. Biochem Pharmacol. 2007; 74(2):336-344.
Martin TJ, Kahn WR, Xiao R, Childers SR. Differential regional effects of methadone maintenance compared to heroin dependence on mu-opioid receptor desensitization in rat brain. Synapse. 2007; 61(3):176-184.
Martin TJ, Eisenach JC, Misler J, Childers SR. Chronic activation of spinal adenosine A1 receptors results in hypersensitivity. Neuroreport. 2006; 17(15):1619-1622.