1. The 5-HT1A
ligand BMY 7378 (8-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]8-azaspirol [4,5]-
decane-7,9-dione dihydrochloride, 0.032-2 mg kg-1, s.c.) caused
hyperphagia, a response to the activation of presynaptic 5-HT1A receptors. 2.
BMY 7378 (8 mg kg-1, s.c.) and the
5-HT1A agonist (8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), 0.10 and 0.25 mg kg-1 s.c.) also caused
hypothermia. This was inhibited by (-)-
pindolol (1-mg kg-1, i.p.) and not prevented by pretreatments with
p-chlorophenylalanine which grossly depleted
5-hydroxytryptamine (5-HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5-HT1A receptors. Infusion of
BMY 7378 (8-64 micrograms) into the dorsal raphe was without convincing hypothermic effect. 3.
BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of postsynaptic 5-HT1A receptors, i.e., the induction of components of the
5-HT syndrome by
8-OH-DPAT (0.5, 1.0 mg kg-1, s.c.) which suggests that
BMY 7378 has antagonistic as well as agonistic effects at these sites. 4. Partial agonist properties of
BMY 7378 at postsynaptic sites were also indicated by doses for
hypothermia being much greater than those for
hyperphagia i.e., ED50 (
hypothermia) greater than 2 mg kg-1, ED50 (
hyperphagia) = 0.010 mg kg-1. This contrasts with the similar ED50 values for both the hypothermic (ED50 = 0.08-0.10 mg kg-1) and hyperphagic (ED50 = 0.06-0.10 mg kg-1) effects of 8-OH-DPAT.5. The evidence obtained for mediation of the hypothermic response to 5-HTIA agonists by postsynaptic sites is relevant to the interpretation of the effects on it of
antidepressant treatments and depressive illness.