Since galanin in vitro selectively increases the KD 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 125I-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 compacta of the substantia nigra, which lacks 5-HT1A binding sites. DPAT (10 nM) reduced the IC50 values of galanin at 125I-galanin binding sites by approximately 55% within all the analyzed di- and telencephalic regions. The overall increase in BO 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 BO 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.(ABSTRACT TRUNCATED AT 250 WORDS)