THE EFFECTS OF SIGMA-LIGANDS AND OF NEUROPEPTIDE-Y ON N-METHYL-D-ASPARTATE-INDUCED NEURONAL ACTIVATION OF CA(3) DORSAL HIPPOCAMPUS NEURONS ARE DIFFERENTIALLY AFFECTED BY PERTUSSIN TOXIN

1 The in vivo effects of the high affinity sigma ligands 1,3-di(2-toly l)guanidine (DTG), (+)-N-cyclopropylmethyl-N-methyl- 1,4-diphenyl-1-et hyl-but-3-en-1-ylamine hydrochloride (JO-17 84), (+)-pentazocine and h aloperidol, 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 unitar y recording, in control rats and in rats pretreated with a local injec tion of pertussis toxin (PTX), to evaluate the possible involvement of G(i/o), proteins in mediating the potentiation of the neuronal respon se to NMDA by the activation of sigma receptors in the dorsal hippocam pus. 2 Microiontophoretic applications as well as intravenous injectio ns of (+)-pentazocine potentiated selectively the NMDA response in con trol rats as well as in PTX-pretreated animals. In contrast, the PTX p retreatment abolished the potentiation of the NMDA response by DTG, JO -1784 and NPY. Moreover, microiontophoretic applications of DTG induce d 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 potenti ation of the NMDA response induced by (+)-pentazocine was suppressed b y haloperidol, whereas the reduction of the NMDA response by DTG was n ot affected by haloperidol.