Naloxone

Naloxone Affinity

Naloxone is a synthetic and nonselective antagonist against all three classic opioid receptors. Structurally, it closely resembles the naturally occurring opiate morphine (Fig. 1). As with morphine, the binding of naloxone to opioid receptors is stereospecific, such that (-)-naloxone (also called l-naloxone for the levorotatory configuration of the asymmetric carbon) binds the -opioid receptor with the same dissociation constant as that for morphine ( 2 x 10-9 M). The affinity of (+)-naloxone...

Limin Mao and John Q Wang 1 Introduction

Phosphorylation of protein kinases and transcription factors represents a major biological mechanism to activate those imperative intracellular effectors. Examination of such phosphorylation in response to extracellular stimulation can assess the functional participation of those proteins in a particular signaling cascade. For example, the Ca2+ signal facilitates the phosphorylation of Ca2+ calmodulin-dependent protein kinase II (CaMKII), a multifunctional protein kinase regulating diverse...

Results in the VTA and Substantia Nigra

Using Western blotting, Nestler and colleagues found increased GluRl levels in the VTA of rats killed 16-18 h after discontinuation of repeated cocaine, morphine, ethanol, or stress paradigms (12,13). Increased GluR1 was not observed in the substantia nigra after repeated cocaine or morphine treatment (12). The substantia nigra was not examined in stress studies (12), but after repeated ethanol administration, there was a greater increase in GluR1 in the substantia nigra than in the VTA (13)....

Habit Learning and Synaptic Plasticity

I turn now to the cellular and molecular mechanisms underlying dopamine-modulated learning in cortex-basal ganglia circuits (see ref. 1). Although the anatomical complexities of such circuits indicate multiple potential loci for plasticity, the cortical projections to striatum have received particular attention. Single striatal neurons sample information from a wide array of cortical cells (103), and it is tempting to consider that plasticity of these synaptic connections might readily serve as...

The Chronic Mouse MPTPProbenecid Model

Pharmacokinetic consideration could be one of the underlying reasons why acute and subacute MPTP injections do not produce a sustained neurological insult in laboratory animals. It has been established that MPTP in rodents, following its peripheral administration, is rapidly excreted through the kidney (62). After reaching the central nervous system (CNS), this toxin and its active metabolite, MPP+, are quickly cleared from the brain (63). Hence, investigators tend to intensify MPTP...

Steffany A L Bennett and David C S Roberts 1 Introduction

The enzyme-linked immunosorbent assay ELISA technique offers a sensitive, simple, and versatile method for quantifying as little as 100 pg of target protein in mixed cell or tissue lysates. A further advantage to the protocol is the ability to process rapidly and reproducibly large numbers of samples with minimal equipment requirements. The underlying principle depends on formation of an antigen-antibody complex immobilized on plastic microtitre plates. Figure 1 illustrates the basic...