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

Abstract

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

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Fig. 1

Overall social activity in adolescent (left panels) and adult (right ▶ panels) rats challenged acutely with vehicle on baseline (solid bars) and MK-801 (top), PEAQX (middle), or ifenprodil (bottom) on test day (hatched bars). Significant differences between baseline and test days are represented by asterisk

Fig. 2

Percent (%) of baseline overall social activity in adolescent and adult rats on test day after challenge with MK-801 (top), PEAQX (middle), or ifenprodil (bottom) Significant differences between adolescents and adults are represented by number sign whereas significant differences from vehicle-treated control group is indicated with a plus sign

Fig. 3

Social preference/avoidance coefficients in adolescent (left ▶ panels) and adult (right panels) rats after MK-801 (top), PEAQX (middle), or ifenprodil (bottom). Significant differences between baseline and test day are represented by asterisk