M. Riad et al., NEUROTROPHIC EFFECTS OF IPSAPIRONE AND OTHER 5-HT1A RECEPTOR AGONISTSON SEPTAL CHOLINERGIC NEURONS IN CULTURE, Developmental brain research, 82(1-2), 1994, pp. 245-258
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.