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Developing axons find their targets through direct contact with cues in the extracellular environment and in response to gradients of diffusible factors. The floor plate, a neuroepithelial structure, guides developing commissural axons in the spinal cord by release of chemoattractants. Floor plate cells express neurokinin-1 receptors, and a transiently appearing subpopulation of commissural axons contains substance P, the neuropeptide ligand for this receptor. Substance P increases the amount of axon outgrowth from dorsal horn explants cocultured with floor plate explants. Results of experiments with embryonic rats suggest that substance P released from pioneering neuronal pathways may regulate the release of chemoattractants from floor plate cells.

Interferon gamma (IFN-gamma) is a pleiotropic lymphokine produced by T-lymphocytes which acts as a soluble mediator in immunological reactions. In addition to several immune target cells, such as monocytes and macrophages, it acts on the principal glial population, the astrocytes, inducing Ia antigen expression. We have developed a binding assay for 125I-labeled recombinant murine IFN-gamma, and show that, using this assay, IFN-gamma interacts with a single specific receptor on the murine astrocyte cell membrane. The binding is specific and saturable and it takes place with a Kd = 1.64 x 10(-9) M, with 11,100 receptor molecules per astrocytic cell. The binding shows, as for macrophages, species specificity. Using an immune assay including rabbit antibodies to IFN-gamma and 125I-labeled protein A, we have demonstrated an internalization of the ligand. This is an energy-dependent process, as around 50% of the bound IFN-gamma is endocytosed after 4 h at 37 degrees C when cultures are maintained in complete culture medium.

The effects of acute treatment or prenatal exposure of rats to antidepressants on locomotor activity and [3H]spiroperidol binding to striatal membranes were studied in 25 day old rats. Prenatal exposure or acute treatment with the antidepressants chlorimipramine, iprindole or mianserin reduced locomotor activity on postnatal day 25. On the contrary, prenatal exposure to nomifensine induced locomotor hyperactivity. It was also found that chlorimipramine, iprindole or nomifensine enhanced the locomotor response to apomorphine. Acute treatment with mianserin, markedly decreased locomotion but in utero mianserin did not modify the apomorphine-induced hyperactivity. Scatchard analysis showed no change in the characteristics of binding of [3H]spiroperidol to striatal dopamine receptors after antidepressant treatment. However, the ability of dopamine to compete for these sites was significantly enhanced after prenatal exposure to all the antidepressants. This increase in agonist affinity for dopamine receptors may explain the long-lasting behavioural supersensitivity of dopamine receptors observed after chronic treatment with typical or atypical antidepressants.