Histamine reduces flash sensitivity of on ganglion cells in the primate retina.

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded with a 16-channel microelectrode array. RESULTS. Low micromolar doses of histamine decreased the rate of maintained firing and the light sensitivity of ON ganglion cells. Both sustained and transient ON cells responded similarly to histamine. There were no statistically significant effects of histamine in a more limited study of OFF ganglion cells. The response latencies of ON cells were approximately 5 ms slower, on average, when histamine was present. Histamine also reduced the signal-to-noise ratio of ON cells, particularly in those cells with a histamine-induced increase in maintained activity. CONCLUSIONS. A major action of histamine released from retinopetal axons under dark-adapted conditions, when rod signals dominate the response, is to reduce the sensitivity of ON ganglion cells to light flashes. These findings may relate to reports that humans are less sensitive to light stimuli in the scotopic range during the day, when histamine release in the retina is expected to be at its maximum.

The opioid antagonist naltrexone and its pharmacological role in treating alcohol dependence: A literature review

Naltrexone, an opioid antagonist, was the second drug approved for treatment of alcohol dependence in the U.S. Its approval followed two landmark studies published in the U.S. in 1992. [1, 2] These studies showed that a combined treatment of naltrexone and behavioral therapy reduced alcohol consumption in alcoholics. Opioid antagonists decrease craving for alcohol and help to reduce drinking by blocking opioid peptide receptors in the body that are active in a dopamine chemical reward system. ^ Despite their usefulness, opioid antagonists have been underutilized. Health providers not educated in the use of opioid antagonists hold the view that opioid antagonist therapy is ineffective. However, it is apparent from the relevant literature that this therapy, when properly understood and targeted, has the potential to make a positive contribution in treating alcohol dependent patients. ^ This thesis will review the scientific literature and the present body of knowledge regarding opioid antagonists (naltrexone) and their pharmacological role in treating alcohol dependence.^