, Volume 231, Issue 8, pp 1797–1807

The effects of an acute challenge with the NMDA receptor antagonists, MK-801, PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats

Original Investigation

DOI: 10.1007/s00213-013-3278-3

Cite this article as:
Morales, M. & Spear, L.P. Psychopharmacology (2014) 231: 1797. doi:10.1007/s00213-013-3278-3



NMDA antagonists consistently produce social inhibition in adult animals, although effects of these manipulations on social behavior of adolescents are relatively unknown.


The aim of this study was to assess potential age differences in the socially inhibitory effects of the non-competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects, given the regional and developmental differences that exist for the NR2 subunit during ontogeny.


In separate experiments, adolescent and adult male Sprague–Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg, i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social interaction test.


Adolescents required higher doses of MK-801 (0.1 and 0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions in social activity after all doses. Likewise, adolescents required higher doses of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to adults (all doses). In contrast, adults were less sensitive to PEAQX than adolescents, with adults showing social inhibition after 20 mg/kg whereas adolescents showed this effect following 10 and 20 mg/kg. Although locomotor activity was generally reduced at both ages by all drugs tested, ANCOVAs using locomotor activity as a covariate revealed similar patterns of social inhibitory effects.


Adolescents are less sensitive than adults to the disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but not by an NR2A antagonist—age differences that may be related to different subunit expression patterns during development.


Social interactionsMK-801PEAQXIfenprodilNMDA antagonistRatAdolescent

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Physiology & PharmacologyWake Forest University School of MedicineWinston-SalemUSA
  2. 2.Center for Development and Behavioral Neuroscience, Department of PsychologyBinghamton UniversityBinghamtonUSA