NEUROTROPHIC EFFECTS OF IPSAPIRONE AND OTHER 5-HT1A RECEPTOR AGONISTSON SEPTAL CHOLINERGIC NEURONS IN CULTURE

Repeated treatment of primary cultures of fetal rat septal neurons wit h 5-HT1A receptor agonists (8-OH-DPAT, ipsapirone, gepirone and buspir one) increased choline acetyltransferase activity after 6-7 days in cu lture. This effect was optimal with ipsapirone (+50-80% at 1 mu M of t he agonist), and could be prevented by potent 5-HT1A receptor antagoni sts such as (-)-tertatolol and (+)-WAY 100135. Under conditions where they completely suppressed the stimulatory effect of NGF on choline ac etyltransferase in these cultures, specific anti-NGF antibodies did no t alter the stimulatory effect of ipsapirone, suggesting that a possib le release of NGF from some septal cells did not account for the effec t of 5-HT1A receptor stimulation. Autoradiographic investigations with [H-3]8-OH-DPAT as radioligand and immunocytochemistry with specific a nti-choline acetyltransferase antibodies and anti-rat 5-HT1A receptor antibodies showed that 5-HT1A receptors were expressed on septal neuro ns in culture, notably on the cholinergic neurons identified by their positive staining with anti-choline acetyltransferase antibodies. Deta iled morphometrical analysis by computer-assisted imaging revealed tha t repeated exposure to ipsapirone (1 mu M for 7 days) did not influenc e the survival of cholinergic as well as non-cholinergic neurons, but specifically altered the neuritic tree (i.e. the total length of neuri tes and the number of branching points) of cholinergic neurons only. T hese data suggest that under in vitro conditions ipsapirone and other 5-HT1A receptor agonists may exert a direct trophic action on septal c holinergic neurons.