Serotonin modulates glutamatergic transmission in the rat olfactory tubercle

The olfactory tubercle (OT) is found in the brains of mammals that are highly dependent on their sense of smell. Its human analogue is the poorly understood anterior perforated substance. Previous work on rat brain slices identified two types of field potential responses from the OT. The association fibre (AF) pathway was sensitive to muscarinic modulation, whereas the lateral olfactory tract (LOT) fibre pathway was not. Here, we establish that serotonin (5-hydroxytryptamine; 5-HT) also inhibits field potential excitatory postsynaptic potentials (EPSPs) in the AF, but not in the LOT fibre, pathway. Parallel experiments with adenosine (ADO) excluded ADO mediation of the 5-HT effect. Exogenous 5-HT at 30 mu m caused a long-lasting similar to 40% reduction in the amplitude of AF postsynaptic responses, without affecting the time-course of EPSP decline, indicating a fairly restricted disposition of the 5-HT receptors responsible. The 5-HT1-preferring, 5-HT5-preferring and 5-HT7-preferring agonist 5-carboxamidotryptamine caused similar inhibition at similar to 100 nm. The 5-HT1A-preferring ligand 8-hydroxy-di-n-propylamino-tetralin at 10 mu m, and the 5-HT uptake inhibitor citalopram at 3 mu m, caused inhibition of AF-stimulated field potential responses in the 5-10% range. Order-of-potency information suggested a receptor of the 5-HT1B or 5-HT1D subtype. The 5-HT1D agonist L-694,247 (1 mu m) suppressed the AF response by similar to 10% when used on its own. After washing out of L-694,427, inhibition by 30 mu m 5-HT was reduced to negligible levels. Allowing for a partial agonist action of L-694,427 and complex interactions of 5-HT receptors within the OT, these results support the presence of active 5-HT1D-type receptors in the principal cell layer of the OT.