Actions of 5-HT1 ligands on excitatory synaptic transmission in the hippocampus of alert rats.
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 microgram). 3. Direct intrahippocampal (i.h.) application of buspirone (ED50 = 0.29 microgram), gepirone (1 microgram), ipsapirone (1 microgram), BMY 7378 (0.1 microgram) and 5-carboxamidotryptamine (5-CT, 0.02 microgram) 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-propylamino) tetralin (8-OH-DPAT, 2 micrograms) and spiroxatrine (1 microgram) 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.
O'Connor
J J
JJ
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.
Rowan
M J
MJ
Anwyl
R
R
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D018492:Dopamine Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D019329:Idazoxan; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009045:Motor Endplate / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014268:Trifluoperazine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018492:Dopamine Antagonists; D010879:Piperazines; D013141:Spiro Compounds; D014268:Trifluoperazine; D012701:Serotonin; C018387:spiroxatrine; C053428:BMY 7378; D002065:Buspirone; D008784:Methysergide; D019329:Idazoxan