RESUMEN
The involvement of neurotensin (NT) within the nucleus accumbens core (NAC) in behavior has been sparsely investigated. Moreover, little is known of what role NT within the ventral striatum has on spatial learning. The present study investigated whether NT receptors in the NAC are implicated in learning of spatial information. Male Long-Evans rats were trained on a food search spatial learning task. Rats were microinfused with either NT antagonist SR 48692 (50 nM/0.5 =L) or saline in the NAC before each training session. Rats treated with SR 48692 made more reference and working memory errors during the acquisition of spatial learning than did rats infused with saline. These results suggest that NT receptors contribute to NAC-mediated spatial learning.
Asunto(s)
Conducta Apetitiva/efectos de los fármacos , Neurotensina/antagonistas & inhibidores , Núcleo Accumbens/efectos de los fármacos , Orientación/efectos de los fármacos , Pirazoles/farmacología , Quinolinas/farmacología , Animales , Ingestión de Alimentos/efectos de los fármacos , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Ratas , Ratas Long-Evans , Receptores de Neurotensina/antagonistas & inhibidoresRESUMEN
A preliminary characterization is provided of a naturally occurring cyclic peptide with interesting and potent biological activity. A 31-residue cyclic peptide, designated cyclopsychotride A [1], was obtained from the organic extract of the tropical plant, Psychotria longipes. Compound 1 inhibited [125I] neurotensin (NT) binding to HT-29 cell membranes (IC50 3 microM) and also stimulated increased levels of cytosolic Ca2+ in two unrelated cell lines that do not express NT receptors. The peptide was found to dose-dependently increase intracellular Ca2+ at concentrations ranging from 3 to 30 microM, and this response was not blocked by a known NT antagonist. Cyclopsychotride A [1] possesses three disulfide linkages and is thought to be the largest cyclic peptide isolated from a natural source. Both 1H-nmr and cd spectroscopy showed 1 to be highly structured.