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Neuropeptide Y and the Calcitonin Gene‐related Peptide Attenuate Learning Impairments Induced by MK‐801 via a Sigma Receptor‐related mechanism
Author(s) -
Bouchard Pascale,
Maurice Tangui,
StPierre Serge,
Privat Alain,
Quirion Rémi
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01381.x
Subject(s) - mechanism (biology) , calcitonin gene related peptide , neuropeptide , receptor , calcitonin , peptide , calcitonin receptor , sigma 1 receptor , neuropeptide y receptor , sigma receptor , neuroscience , gene , sigma , chemistry , pharmacology , endocrinology , medicine , psychology , microbiology and biotechnology , biology , biochemistry , physics , agonist , quantum mechanics
It has been shown recently that low doses of sigma (σ) receptor ligands like 1,3‐di‐(2‐tolyl)guanidine (DTG), (+) N ‐allylnormetazocine [(+)SKF 10 047] and (+)pentazocine can antagonize learning impairments induced by dizocilpine (MK‐801), a non‐competitive antagonist at the NMDA receptor channel. This antagonism has been proposed to involve σ receptor sites since it is blocked by the administration of purported o antagonists such as NE‐100 and BMY‐14802. It has also been demonstrated that peptides of the neuropeptide Y (NPY) and calcitonin gene‐related peptide (CGRP) families modulate, in vivo , é labelling and electrophysiological effects in the hippocampal formation. Accordingly, we investigated if NPY‐ and CGRP‐related peptides modulate cognitive processes by interacting with σ sites in mice. In order to test this hypothesis, a step‐down passive avoidance task was used. Interestingly, similarly to various σ agonists, NPY, peptide YY (PYY) and the Y 1 agonist [Leu 31 Pro 34 ]NPY (but not NPY13–36, a purported Y 2 agonist), as well as hCGRPα and the purported CGRP 2 agonist [CyS(ACM) 2–7 ]hCGRPα (but not CGRP 8–37 , a CGRP 1 receptor antagonist), significantly attenuated learning impairments induced by MK‐801. Furthermore, the effects of NPY, [Leu 31 Pro 34 ]NPY, hCGRPα and [CYS(ACM) 2–7 ]hCGRPα were blocked by the administration of the σ antagonist, BMY‐14802. The present data suggest that NPY‐ and CGRP‐related peptides can indirectly interact in vivo with σ receptors to modulate cognitive processes associated with NMDA receptor function.