Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats

Abstract

1. The effects of 5-hydroxytryptamine1 (5-HT1) ligands on excitatory synaptic transmission were examined in the stratum radiatum of the CA1 region of the dorsal hippocampus of alert, gently restrained, rats. 2. 5-HT produced a dose-dependent reduction in the amplitude of the electrically evoked population excitatory postsynaptic potential (e.p.s.p.) when injected directly into the hippocampus via a cannula (dose producing 50% maximum inhibition, ED50 = 0.46 μg). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 μg), gepirone (1 μg), ipsapirone (1 μg), BMY 7378 (0.1 μg) and 5-carboxamidotryptamine (5-CT, 0.02 μg) mimicked the inhibitory effect of 5-HT. 4. Systemic injection of buspirone (ED50 = 0.88 mg kg-1, i.p.), BMY 7378 (0.01 mg kg-1, i.p.) and RU 24969 (1 mg kg-1, s.c.) also had an inhibitory effect on the amplitude of the e.p.s.p. 5. Injection of 8-hydroxy-2-(di-n-propylamine) tetralin (8-OH-DPAT, 2 μg) and spiroxatrine (1 μg) i.h. alone had no effect on the e.p.s.p. amplitude but prevented the inhibitory effect of 5-HT. 6. Systemic injection (i.p.) of methysergide (5 mg kg-1) and spiroxatrine (1 mg kg-1) antagonized the inhibitory effect of buspirone whereas pretreatment with ketanserin (1 mg kg-1), trifluoperazine (1 mg kg-1) and idazoxan (1 mg kg-1) had no effect on the response to buspirone. 7. It is concluded that hippocampal synaptic transmission is highly sensitive to the agonist and antagonist properties of 5-HT1 ligands in the alert rat.