Feeding-induced increase in the extracellular concentration of histamine in rat hypothalamus as measured by in vivo microdialysis

Department of Pharmacology, Okayama University, Okayama, Okayama, Japan
Neuroscience Letters (Impact Factor: 2.06). 05/1991; 125(2):235-237. DOI: 10.1016/0304-3940(91)90037-T

ABSTRACT The extracellular concentration of histamine (HA) in the hypothalamus of conscious and freely moving rats was measured by in vivo microdialysis and the effects of fasting and feeding on the HA concentration were examined. In non-fasted rats, the basal HA concentration was almost constant from 11.00 to 17.00 h on the day following implantation of the dialysis probe, the mean value being . No significant change in the HA concentration was observed in rats deprived of food for 24 h. In 24-h fasted rats, feeding for 15 min produced a transient and significant increase in the HA concentration. These results suggest that histaminergic activity in the rat hypothalamus increases during feeding.

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    ABSTRACT: BACKGROUND AND PURPOSE Centrally acting histamine H(3) receptor ligands are proposed as potential treatments for obesity, although the value of inverse agonists at these receptors is still debated. Functional inhibition of H(3) autoreceptors activates neurones in a hypothalamic 'satiety' centre. The H(3) receptor antagonist, proxyfan was used as a tool to assess the action of histaminergic compounds in this model. EXPERIMENTAL APPROACH We compared the actions of histamine on feeding with those of an H(3) receptor agonist (imetit) and inverse agonist (thioperamide) in rats and mice. Sites of action were identified by immunohistochemistry and the hypothalamic ventromedial nucleus (VMN) was investigated using electrophysiological techniques. KEY RESULTS Central histamine or thioperamide decreased fast-induced feeding, whereas imetit increased feeding. Systemic thioperamide entered the brain to activate hypothalamic feeding centres and to reduce feeding without causing any adverse behaviours. Thioperamide activated neurones in the VMN through an action on histamine autoreceptors, whilst imetit had the opposite effect. Proxyfan administered alone did not affect either feeding or electrical activity. However, it blocked the actions of both thioperamide and imetit, acting as a neutral antagonist in this system. CONCLUSIONS AND IMPLICATIONS The H(3) receptor inverse agonist, thioperamide, potently reduced appetite without adverse behavioural effects. This action was blocked by proxyfan, acting as a neutral antagonist in this model and, therefore, this compound is useful in determining the selectivity of H(3) receptor-directed drugs. A major action of thioperamide is through presynaptic autoreceptors, inducing stimulation by endogenous histamine of postsynaptic H(1 ) receptors on anorectic hypothalamic neurones.
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    Frontiers in Systems Neuroscience 05/2012; 6:44. DOI:10.3389/fnsys.2012.00044
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