TY - JOUR
T1 - Polyamines inhibit N-methyl-d-aspartate antagonist-induced darting behavior in the rat prefrontal cortex
AU - Crawley, Jacqueline N.
AU - Evers, John R.
AU - Paul, Steven M.
PY - 1992/7/17
Y1 - 1992/7/17
N2 - The competitive NMDA (N-methyl-d-aspartate) receptor antagonist, CPP (3(2-carboxypiperazin-4-yl)-propyl-1-phophonic acid), microinjected into the medial prefrontal cortex of rats, induces a unique behavioral syndrome termed 'darting', characterized by rapid leaping across an open field arena15. In addition, CPP induces generalized hyperactivity when microinjected into the medial prefrontal cortex, nucleus accumbens, and caudate nucleus. Polyamine modulation of the NMDA receptor was tested at the medial prefrontal cortex microinjection site in this behavioral paradigm. The polyamine spermidine, and its diamine precursor, blocked CPP-induced darting behavior, as well as CPP-induced hyperactivity, at doses which did not decrease locomotor activity when administered alone. The putative polyamine antagonists, ifenprodil and diethylenetriamine, did not prevent spermidine from inhibiting CPP-induced darting. These results suggest that polyamines, presumably by acting as positive allosteric modulators of the NMDA receptor, can inhibit the CPP-induced behavioral syndrome at the prefrontal cortex site.
AB - The competitive NMDA (N-methyl-d-aspartate) receptor antagonist, CPP (3(2-carboxypiperazin-4-yl)-propyl-1-phophonic acid), microinjected into the medial prefrontal cortex of rats, induces a unique behavioral syndrome termed 'darting', characterized by rapid leaping across an open field arena15. In addition, CPP induces generalized hyperactivity when microinjected into the medial prefrontal cortex, nucleus accumbens, and caudate nucleus. Polyamine modulation of the NMDA receptor was tested at the medial prefrontal cortex microinjection site in this behavioral paradigm. The polyamine spermidine, and its diamine precursor, blocked CPP-induced darting behavior, as well as CPP-induced hyperactivity, at doses which did not decrease locomotor activity when administered alone. The putative polyamine antagonists, ifenprodil and diethylenetriamine, did not prevent spermidine from inhibiting CPP-induced darting. These results suggest that polyamines, presumably by acting as positive allosteric modulators of the NMDA receptor, can inhibit the CPP-induced behavioral syndrome at the prefrontal cortex site.
KW - Allosteric neuromodulator
KW - Darting behavior
KW - Hyperlocomotion
KW - NMDA receptor
KW - Polyamine
KW - Prefrontal cortex
UR - http://www.scopus.com/inward/record.url?scp=0026744523&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(92)91364-K
DO - 10.1016/0006-8993(92)91364-K
M3 - Article
C2 - 1511351
AN - SCOPUS:0026744523
SN - 0006-8993
VL - 586
SP - 6
EP - 11
JO - Brain Research
JF - Brain Research
IS - 1
ER -