Glucocorticoid receptor antagonism disrupts the reconsolidation of social reward-related memories in rats

Abstract

Reconsolidation is the process whereby consolidated memories are destabilized upon retrieval and restabilized to persist for later use. Although the neurobiology of the reconsolidation of both appetitive and aversive memories has been intensively investigated, reconsolidation of memories of physiologically relevant social rewards has received little attention. Social play, the most characteristic social behaviour displayed by young mammals, is highly rewarding, illustrated by the fact that it can induce conditioned place preference (CPP). Here, we investigated the role of signalling mechanisms implicated in memory processes, including reconsolidation, namely glucocorticoid, mineralocorticoid, NMDA glutamatergic and CB1 cannabinoid receptors, in the reconsolidation of social play-induced CPP in rats. Systemic treatment with the glucocorticoid receptor antagonist mifepristone before, but not immediately after, retrieval disrupted the reconsolidation of social play-induced CPP. Mifepristone did not affect social play-induced CPP in the absence of memory retrieval. Treatment with the NMDA receptor antagonist MK-801 modestly affected the reconsolidation of social play-induced CPP. However, the reconsolidation of social play-induced CPP was not affected by treatment with the mineralocorticoid and CB1 cannabinoid receptor antagonists spironolactone and rimonabant, respectively. We conclude that glucocorticoid neurotransmission mediates the reconsolidation of social reward-related memories in rats. These data indicate that the neural mechanisms of the reconsolidation of social reward-related memories only partially overlap with those underlying the reconsolidation of other reward-related memories.

Figure 1

(A) Effects of pre- and post-retrieval mifepristone (RU486; RU) on social play-induced CPP. The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test, CS+: conditioning session with a play-partner, CS−: conditioning session alone). Data represent the mean time (s + SEM) spent in the social compartment (grey and black bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test- (TEST) and reinstatement- (REIN) sessions. Vehicle-treated animals (VEH: 2 ml/kg, s.c., n= 32), mifepristone-treated animals (30 mg/kg, s.c., treatment pre-retrieval: Rupre, n=:9; treatment post-retrieval: Rupost: n= 24). (B) Effects of mifepristone on social play-induced CPP in the absence of memory-retrieval. Vehicle-treated animals (VEH; 2ml/kg, i.p., n= 6), mifepristone-treated animals (RU, 30 mg/kg, i.p., n= 10). Post-hoc Student's paired t-tests for difference in time spent in the social- and non-social compartment *p<0.05, **p<0.01, ***p<0.001.

Figure 2

Effects of pre- and post-retrieval spironolactone on social play-induced CPP. The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test, CS+: conditioning session with a play-partner, CS−: conditioning session alone). Data represent the mean time (s + SEM) spent in the social compartment (grey and black bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test- (TEST) and reinstatement- (REIN) sessions. Vehicle-treated animals (VEH: 2 ml/kg, s.c., n= 12), spironolactone-treated animals (30 mg/kg, s.c., treatment pre-retrieval: Sprlpre: n= 10; treatment post-retrieval Sprlpost:, n= 7).

Figure 3

Effects of MK-801 treatment on social play-induced CPP. The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test, CS+: conditioning session with a play-partner, CS-: conditioning session alone). Data represent the mean time (s + SEM) spent in the social compartment (grey and black bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test- (TEST) and reinstatement- (REIN) sessions. (A) Effects of pre- and post-retrieval MK-801 (0.1 mg/kg). Vehicle-treated animals (VEH: 2 ml/kg, s.c., n= 40), MK-801-treated animals (0.1 mg/kg, i.p., treatment pre-retrieval: Mkpre:, n= 29; treatment post-retrieval: Mkpost: n= 19). Post-hoc Student's paired t-tests for difference in time spent in the social- and non-social compartment *p<0.05, **p<0.01, ***p<0.001. (B) Effects of post-retrieval MK-801 (0.2 mg/kg). Vehicle-treated animals (VEH: 2 ml/kg, i.p., n= 8), MK-801-treated animals (0.2 mg/kg, i.p., MKpost: n= 8).

Figure 4

(A) Effects of pre- and post-retrieval rimonabant (SR141716; SR) on social play-induced CPP. The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test, CS+: conditioning session with a play-partner, CS-: conditioning session alone). Data represent the mean time (s + SEM) spent in the social compartment (grey and black bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test- (TEST) and reinstatement- (REIN) sessions. Vehicle-treated animals (VEH: 2 ml/kg, i.p., n= 19), rimonabant-treated animals (1.0 mg/kg, i.p., treatment pre-retrieval: SRpre: n= 10; treatment post-retrieval: SRpost: n= 8). (B) Time spent scratching during the 15 min test in pre-retrieval rimonabant-treated animals. Independent samples t-test, *p<0.05.