B Reed

Publications (2)7.95 Total impact

• Article: Bidirectional translational research: Progress in understanding addictive diseases.

  M J Kreek, S D Schlussman, B Reed, Y Zhang, D A Nielsen, O Levran, Y Zhou, E R Butelman
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  ABSTRACT: The focus of this review is primarily on recent developments in bidirectional translational research on the addictions, within the Laboratory of the Biology of Addictive Diseases at The Rockefeller University. This review is subdivided into major interacting aspects, including (a) Investigation of neurobiological and molecular adaptations (e.g., in genes for the opioid receptors or endogenous neuropeptides) in response to cocaine or opiates, administered under laboratory conditions modeling chronic patterns of human self-exposure (e.g., chronic escalating "binge"). (b) The impact of such drug exposure on the hypothalamic-pituitary-adrenal (HPA) axis and interacting neuropeptidergic systems (e.g., opioid, orexin and vasopressin). (c) Molecular genetic association studies using candidate gene and whole genome approaches, to define particular systems involved in vulnerability to develop specific addictions, and response to pharmacotherapy. (d) Neuroendocrine challenge studies in normal volunteers and current addictive disease patients along with former addicts in treatment, to investigate differential pharmacodynamics and responsiveness of molecular targets, in particular those also investigated in the experimental and molecular genetic approaches as described above.
  Neuropharmacology 09/2008; 56 Suppl 1:32-43. · 4.81 Impact Factor
• Article: Extracellular biotransformation of beta-endorphin in rat striatum and cerebrospinal fluid.

  B Reed, J M Bidlack, B T Chait, M J Kreek
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  ABSTRACT: Numerous studies have investigated the behavioural effects of beta-endorphin, both endogenous and exogenously applied. However, the potential for biotransformation of beta-endorphin in the extracellular space of the brain has not been previously directly addressed in vivo. Utilising microinfusion/microdialysis and matrix-assisted laser desorption/ionisation mass spectrometry, we investigated beta-endorphin biotransformation in the striatum of rats. We infused 1.0 nmol beta-endorphin into the striatum of adult male Fischer rats and observed rapid cleavage resulting in beta-endorphin 1-18, as well as several fragments resulting from further N-terminal degradation. In vitro studies with incubation of full-length beta-endorphin, with and without protease inhibitors, in the incubation fluid of isolated striatal slices indicate that beta-endorphin is initially cleaved predominantly at the Phe(18)-Lys(19), position, as well as at the Leu(17)-Phe(18) position. Investigations of cerebrospinal fluid revealed similar enzymatic cleavage of beta-endorphin. The observed pattern of cleavage sites (Phe(18)-Lys(19) and Leu(17)-Phe(18)) is consistent with published in vitro studies of purified insulin-degrading enzyme cleavage of beta-endorphin. The binding affinities of full-length beta-endorphin, as well as previously identified beta-endorphin fragments alpha-endorphin (beta-endorphin 1-16) and gamma-endorphin (beta-endorphin 1-17), and the fragment identified in the present study, beta-endorphin 1-18, at heterologously expressed mu, delta and kappa-opioid receptors, respectively, were determined; the affinity of the truncation fragments is reduced at each of the receptors compared to the affinity of full length beta-endorphin.
  Journal of Neuroendocrinology 06/2008; 20(5):606-16. · 3.14 Impact Factor