PHARMACOLOGICAL CHARACTERIZATION, ANATOMICAL DISTRIBUTION AND SEX-DIFFERENCES OF THE NON-NMDA EXCITATORY AMINO-ACID RECEPTORS IN THE QUAIL BRAIN AS IDENTIFIED BY CNQX BINDING

The distribution of non-N-methyl-D-aspartate binding sites was studied in coronal and sagittal sections through the brain of adult Japanese quail by quantitative autoradiography, using tritiated 6-cyano-7-nitro quinoxaline-2,3-dione as a radioligand. Saturation binding experiments were, in addition, carried out in areas showing high levels of bindin g (cerebellar molecular layer, nucleus anterior medialis and nucleus i nfundibularis) and demonstrated that the binding of tritiated ligand w as specific and saturable. Competition studies with alpha-amino-3-hydr oxy-methyl-4-isoxazole propionic acid and kainic acid indicated that k ainic acid strongly inhibited ligand binding in all brain areas. alpha -Amino-3-hydroxy-methyl-4-isoxazole propionic acid was only a weak inh ibitor in the hypothalamic nuclei whereas in the cerebellar molecular layer both high and low affinity inhibitions were detected. The highes t binding levels of tritiated ligand were observed in the molecular la yer of the cerebellum. Very high levels of binding were detected in va rious preoptic/hypothalamic sites including the nucleus suprachiasmati cus pars medialis, nucleus anterior medialis hypothalami, nucleus infu ndibularis, nucleus mammillaris medialis, nucleus posteromediale hypot halami and nucleus hypothalami ventromedialis. High levels of binding were also detected in the bulbus olfactorius, bed nucleus commissurali s anterior, bed nucleus commissuralis pallii, nucleus accumbens, bed n ucleus striae terminalis and nucleus interpeduncularis. In the preopti c area/hypothalamus, high levels of binding were clearly present in al l areas that contain gonadotropin releasing hormone cells or fibers. I n the pens and mesencephalon, moderate levels of binding were associat ed with catecholaminergic areas such as the area ventralis tegmentalis (area ventralis of Tsai) and the locus coeruleus. Saturation analysis demonstrated the presence of a higher number of binding sites in fema les than in males in the cerebellar molecular layer, nucleus infundibu laris and nucleus anterior medialis. This latter difference was confir med in the one point assays that also identified higher levels of spec ific binding in the nucleus suprachiasmaticus pars medialis of males a s compared with females. These anatomical data suggest a possible impl ication of non-N-methyl-D-aspartate receptors in the synthesis and/or release of both gonadotropin releasing hormone and catecholaminergic n eurotransmitters that should now be tested by pharmacological experime nts. (C) 1998 Elsevier Science B.V. All rights reserved.