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The effects of sigma ligands and of neuropeptide Y on N‐methyl‐ d ‐aspartate‐induced neuronal activation of CA 3 dorsal hippocampus neurones are differentially affected by pertussin toxin
Author(s) -
Monnet François P.,
Debonnel Guy,
Bergeron Richard,
Gronier Benjamin,
Montigny Claude
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13134.x
Subject(s) - nmda receptor , long term potentiation , neuropeptide y receptor , haloperidol , chemistry , sigma receptor , pharmacology , glutamatergic , receptor , neuropeptide , endocrinology , biology , glutamate receptor , dopamine , biochemistry
1 The in vivo effects of the high affinity sigma ligands 1,3‐di(2‐tolyl)guanidine (DTG), (+)‐N‐cyclopropylmethyl‐ N ‐methyl‐1,4‐diphenyl‐1‐ethyl‐but‐3‐en‐1‐ylamine hydrochloride (JO‐1784), (+)‐pentazocine and haloperidol, as well as of those of neuropeptide Y (NPY), on N ‐methyl‐ d ‐aspartate (NMDA)‐ and quisqualate (Quis)‐induced neuronal activations of CA 3 pyramidal neurones were assessed, using extracellular unitary recording, in control rats and in rats pretreated with a local injection of pertussis toxin (PTX), to evaluate the possible involvement of G i/o proteins in mediating the potentiation of the neuronal response to NMDA by the activation of sigma receptors in the dorsal hippocampus. 2 Microiontophoretic applications as well as intravenous injections of (+)‐pentazocine potentiated selectively the NMDA response in control rats as well as in PTX‐pretreated animals. In contrast, the PTX pretreatment abolished the potentiation of the NMDA response by DTG, JO‐1784 and NPY. Moreover, microiontophoretic applications of DTG induced a reduction of NMDA‐induced neuronal activation. Neither in control nor in PTX‐treated rats, did the sigma ligands and NPY have any effect on Quis‐induced neuronal response. 3 In PTX‐treated rats, the potentiation of the NMDA response induced by (+)‐pentazocine was suppressed by haloperidol, whereas the reduction of the NMDA response by DTG was not affected by haloperidol. 4 This study provides the first in vivo functional evidence that sigma ligands and NPY modulate the NMDA response by acting on distinct receptors, differentiated by their PTX sensitivity.