1. The Distribution of Histamine in the CNS Is Widespread

HA neurons, originating in five nuclei within the tuberomamillary nucleus of the hypothalamus, innervate almost every structure in the brain stem and cerebral cortices. The densest innervation is to the hypothalamus and septum. Somewhat lower densities are found in the cortex and amygdala, and the lowest is seen in the hippocampus, brain stem, and cerebellum. At least three types of HA receptors (H1-H3) have been identified in the brain. In addition, HA is present in nonneural mast cells of the brain.

2. The Cellular Effects of HA Resemble Those of NA and ACH

The effects of HA on cells can be inhibitory or excitatory, like the majority of NMTs. Although the ionic mechanisms of these effects are less well-known than those of NA or ACH, at least some of the excitation is produced by reductions in K+ currents, leading to a faster recovery after an action potential. For example, application of H2 agonists to thalamic and cortical neurons causes excitation by reducing the afterhyperpolarization currents; H1 agonists may increase excitation by producing slow depolarizations. However, H3 receptors are probably located on histaminergic terminals and limit HA release by autoreceptor inhibition.

3. Histamine's Action Depends on the Receptors It Stimulates

HA administered intravenously or intracerebrally induces an EEG arousal response and spontaneous locomotor behavior, including exploration and grooming. These changes are blocked by H1 antagonists, an effect consistent with the cellular effects of these drugs. H3 agonists cause animals to spend a longer amount of time in SWS and the increased time can be blocked by either H3 agonists or H1 antagonists.

The dynamics of the cortical EEG are mediated normally by thalamic mechanisms. Application of HA to thalamic neurons results in a slow depolarization of the membrane produced by reductions in K+ currents. This switches synchronized activity of individual neurons to the single-spike mode of repetitive firing. Recent evidence indicates that HA's major contribution is to the regulation of arousal rather than the control of alerting or vigilance.

Part of HA's effects may be due to interactions with cholinergic neurons of the basal forebrain and later-odorsal tegmentum as well as the LC. Application of HA excites basal forebrain and tegmental cholinergic neurons through stimulation of H1 and H2 receptors. These findings suggest that ACH and HA may synergistically increase cellular and behavioral arousal.

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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