Elsevier

Brain Research

Volume 560, Issues 1–2, 27 September 1991, Pages 251-259
Brain Research

Activation of 5-hydroxytryptamine1A receptors increases the affinity of galanin receptors in di- and telencephalic areas of the rat

https://doi.org/10.1016/0006-8993(91)91240-2Get rights and content

Abstract

Since galanin in vitro selectively increases theKD value of 5-HT1A receptors without altering the binding of 5-HT1B or 5-HT2 receptors, we have studied whether 5-HT1A receptor activation in turn may affect galanin binding in the ventral di- and telencephalon and the substantia nigra of the rat. As analyzed by autoradiography, the binding of125I-galanin was increased by about 55% in the presence of 3–30 nM of 8-OH-2-(di-npropylamino)-tetralin (DPAT) in the paraventricular thalamic nucleus, the nucleus reuniens and rhomboideus, the zona incerta, the medial and the lateral hypothalamus, and the medial and the lateral amygdaloid area, but not in the pars compacta of the substantia nigra, which lacks 5-HT1A binding sites. DPAT (10 nM) reduced the IC50 values of galanin at125I-galanin binding sites by approximately 55% within all the analyzed di- and telencephalic regions. The overall increase inBO values was50 ± 11%. Using the filter wipe technique in cryostat sections at Bregma -2.8 mm covering all the brain regions at this level, DPAT (10 nM) decreased the IC50 values of galanin from21.6 ± 1.1nM (control) to15.5 ± 0.9nM, and increased theBO values by19.4 ± 4.1%. In membrane preparations from the ventral di- and telencephalon, DPAT decreased the IC50 values of galanin binding sites by20 ± 3% at 100 nM of DPAT. This effect could be completely blocked by the specific 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine. GTP (0.1 nM) produced a17 ± 5% increase in the IC50 value of galanin and a23 ± 4% decrease in theBO value of125I_galanin binding sites. However, DPAT (100 nM) was still able to decrease the IC50 values of galanin in the presence of GTP (-8 ± 3%;control-10 ± 3%). TheBmax value of125I-galanin binding was not affected by DPAT. The increased affinity of galanin binding sites by DPAT seems to reflect a G-protein-independent intramembrane receptor-receptor interaction between 5-HT1A and galanin receptors. This interaction may represent an intramembrane inhibitory feed-back mechanism of 5-HT1A receptor sensitivity, and may be important both under normal conditions and in 5-HT-mediated mental disorders.

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