β-Adrenoreceptor stimulation mediates reconsolidation of social reward-related memories

Abstract

Background: In recent years, the notion that consolidated memories become transiently unstable after retrieval and require reconsolidation to persist for later use has received strong experimental support. To date, the majority of studies on reconsolidation have focused on memories of negative emotions, while the dynamics of positive memories have been less well studied. Social play, the most characteristic social behavior displayed by young mammals, is important for social and cognitive development. It has strong rewarding properties, illustrated by the fact that it can induce conditioned place preference (CPP). In order to understand the dynamics of positive social memories, we evaluated the effect of propranolol, a β-adrenoreceptor antagonist known to influence a variety of memory processes, on acquisition, consolidation, retrieval and reconsolidation of social play-induced CPP in adolescent rats.

Methodology/principal findings: Systemic treatment with propranolol, immediately before or after a CPP test (i.e. retrieval session), attenuated CPP 24 h later. Following extinction, CPP could be reinstated in saline--but not in propranolol-treated rats, indicating that propranolol treatment had persistently disrupted the CPP memory trace. Propranolol did not affect social play-induced CPP in the absence of memory retrieval or when administered 1 h or 6 h after retrieval. Furthermore, propranolol did not affect acquisition, consolidation or retrieval of social play-induced CPP.

Conclusions/significance: We conclude that β-adrenergic neurotransmission selectively mediates the reconsolidation, but not other processes involved in the storage and stability of social reward-related memories in adolescent rats. These data support the notion that consolidation and reconsolidation of social reward-related memories in adolescent rats rely on distinct neural mechanisms.

Figure 1. Effects of acute post-retrieval PROP 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 (sec ± SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test- (TEST) and reinstatement- (REIN) sessions. Saline-treated animals (2 ml/kg, i.p., n = 18), PROP-treated animals (10 mg/kg, i.p., n = 8). 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 1h and 6h delayed post-retrieval PROP on reconsolidation of 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 (sec ± SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR) and test- (TEST) sessions. Saline-treated animals (2 ml/kg, i.p., n = 17), 1 h delayed PROP-treated animals (10 mg/kg, i.p., n = 13), 6 h delayed PROP-treated animals (10 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 3. Effects of PROP on social play-induced CPP in the absence of memory-retrieval.

The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test). Data represent the mean time (sec ± SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during a 15 min test session. Saline-treated animals (2 ml/kg, i.p., n = 16), PROP-treated animals (10 mg/kg, i.p., n = 16). Post-hoc Student's paired t-tests for difference in time spent in the social- and non-social compartment **p<0.01.

Figure 4. Effects of PROP on memory-retrieval of 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 (sec ± SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during 15 min retrieval- (RETR), test-(TEST) and reinstatement- (REIN) sessions. Saline-treated animals (2 ml/kg, i.p., n = 22), PROP-treated animals (10 mg/kg, i.p., n = 15). 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 5. Effects of PROP on acquisition (panel A) and consolidation (panel B) of social play-induced CPP.

The experimental protocol is depicted above the graph (Pre-C: pre-conditioning test, CS: daily conditioning sessions, consisting of one session with and one session without a play-partner present). PROP was administered either 30 min before (acquisition) or immediately after (consolidation) each conditioning session. Data represent the mean time (sec ± SEM) spent in the social compartment (grey bars) and the non-social compartment (white bars) during a 15 min retrieval-session. Saline-treated animals (2 ml/kg, i.p., acquisition: n = 16, consolidation: n = 12), PROP-treated animals (10 mg/kg, i.p., acquisition: n = 16, consolidation: n = 12). Post-hoc Student's paired t-tests for difference in time spent in the social- and non-social compartment **p<0.01, ***p<0.001.