Activation of 5-hydroxytryptamine 1A receptors increases the affinity of galanin receptors in di- and telencephalic areas of the rat

Abstract

Since galanin in vitro selectively increases the K D value of 5-HT 1A receptors without altering the binding of 5-HT 1B or 5-HT 2 receptors, we have studied whether 5-HT 1A 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 of 125I-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-HT 1A binding sites. DPAT (10 nM) reduced the IC 50 values of galanin at 125I-galanin binding sites by approximately 55% within all the analyzed di- and telencephalic regions. The overall increase in B O values was 50 ± 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 IC 50 values of galanin from 21.6 ± 1.1nM (control) to 15.5 ± 0.9nM, and increased the B O values by 19.4 ± 4.1%. In membrane preparations from the ventral di- and telencephalon, DPAT decreased the IC 50 values of galanin binding sites by 20 ± 3% at 100 nM of DPAT. This effect could be completely blocked by the specific 5-HT 1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine. GTP (0.1 nM) produced a 17 ± 5% increase in the IC 50 value of galanin and a 23 ± 4% decrease in the B O value of 125I_galanin binding sites. However, DPAT (100 nM) was still able to decrease the IC 50 values of galanin in the presence of GTP ( -8 ± 3%;control-10 ± 3%). The B max value of 125I-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-HT 1A and galanin receptors. This interaction may represent an intramembrane inhibitory feed-back mechanism of 5-HT 1A receptor sensitivity, and may be important both under normal conditions and in 5-HT-mediated mental disorders.