ACTIVATION OF 5-HYDROXYTRYPTAMINE-1A RECEPTORS INCREASES THE AFFINITY OF GALANIN RECEPTORS IN DIENCEPHALIC AND TELENCEPHALIC AREAS OF THE RAT

Since galanin in vitro selectively increases the K(D) 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 of I-125-galanin was increased by about 55% in the presence of 3-30 nM of 8-OH-2-(di-n-propylamino)-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 compacts of the substantia nigra, which lacks 5-HT1A binding sites. DPAT (10 nM) reduced the IC50 values of galanin at I-125-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 IC50 values of galanin from 21.6 +/- 1.1 nM (control) to 15.5 +/- 0.9 nM, and increased the B(O) values by 19.4 +/- 4.1%. In membrane preparations from the ventral di- and telencephalon, DPAT decreased the IC50 values of galanin binding sites by 20 +/- 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-phthalimido)butyl]piperazine. GTP (0.1 mM) produced a 17 +/- 5% increase in the IC50 value of galanin and a 23 +/- 4% decrease in the B(O) value of I-125-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%). The B(max) value of I-125-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.