MODULATION BY DOPAMINE-RECEPTORS OF THE HISTAMINE-RELEASE IN THE RAT HYPOTHALAMUS

The involvement of dopaminergic neurons of the hypothalamus in the modulation of histamine release was studied by the push-pull technique. The posterior hypothalamus of the conscious, freely moving rat was superfused with artificial cerebrospinal fluid (CSF) and the release of histamine was determined radioenzymatically in the superfusate. Agonists and antagonists of dopamine D1-, D2- and D3-receptors were dissolved in CSF and applied to the hypothalamus through the push-pull cannula. Hypothalamic superfusion with the D1-, D2- and D3-receptor agonists dopamine or R(-)-apomorphine enhanced the release rate of histamine. (+/-)-Apomorphine also enhanced the release of histamine, but to a lesser extent than did equimolar concentration of R(-)-apomorphine. The D3-agonist quinpirole inhibited the release of histamine, while the D1-receptor agonist SKF 82958 [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] did not virtually influence the release of the neurotransmitter. On the other hand, [-]-sulpiride which predominantly blocks D2-receptors, decreased histamine release. Hypothalamic superfusion with SKF 83566 [(+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], which seems to be a selective antagonist of D1-receptors, enhanced the release rate of histamine. These findings suggest that dopaminergic neurons of the hypothalamus influence the release of histamine from its neurons in a dual way. D2-heteroreceptors stimulate the release of histamine, while D3-heteroreceptors seem to inhibit the release of this neurotransmitter. Both types of dopamine receptors might be located presynaptically on histaminergic neurons. Alternatively, D3- and D2-receptors might be located on histaminergic and non-histaminergic neurons, respectively.