Reconsolidation of appetitive memories for both natural and drug reinforcement is dependent on β-adrenergic receptors

Abstract

We have investigated the neurochemical mechanisms of memory reconsolidation and, in particular, the functional requirement for intracellular mechanisms initiated by ␤-adrenergic signaling. We show that propranolol, given in conjunction with a memory reactivation session, can specifically disrupt the conditioned reinforcing properties of a previously appetitively reinforced conditioned stimulus (CS), whether the stimulus had been associated with self-administered cocaine or with sucrose. These data show that memories for both drug and nondrug CS-US associations are dependent on ␤-adrenergic receptor-mediated signaling for their reconsolidation, with implications for the potential development of a novel treatment for drug addiction and some forms of obesity.The neurochemical mechanisms underlying memory reconsolidation-the process hypothesized to occur following the reactivation or retrieval of a fully consolidated memory upon reexposure to conditioned stimuli (Nader 2003; Dudai and Eisenberg 2004)-have become increasingly investigated, in part because of the emergence of the view that disrupting memory reconsolidation might be exploited to treat neuropsychiatric disorders based upon the existence of maladaptive memories (e.g., Debiec and LeDoux 2006).Adrenergic signaling is implicated in both memory consolidation and reconsolidation; the administration of adrenaline enhances memory consolidation in aversive and appetitive tasks in animals and humans (Gold et al. 1977;Liang et al. 1985;Sternberg et al. 1985;Introini-Collison and McGaugh 1986), and the administration of adrenergic receptor antagonists induces memory deficits in tasks including inhibitory avoidance (Lennartz et al. 1996), taste memory (Miranda et al. 2003), and odor-reward associations (Wilson et al. 1994) in rats and, in humans, fear memory (Grillon et al. 2004) and emotional learning (Cahill et al. 1994;van Stegeren et al. 1998). In rodents, ␤-adrenergic signaling has also been implicated in the reconsolidation of CS-fear memories (Debiec and LeDoux 2004), drugassociated memories (Bernardi et al. 2006), spatial memories (Przybyslawski et al. 1999), and other forms of appetitive memory (Diergaarde et al. 2006). However, although the administration of ␤-adrenergic receptor antagonists has been shown to disrupt appetitive memories in both a cocaine-conditioned place preference (Bernardi et al. 2006) and a context-induced sucroseseeking task (Diergaarde et al. 2006), it remains unclear whether CS-food memories undergo reconsolidation in a similar manner to CS-addictive drug associations.It has been proposed that drug-associated memories may be mediated by the same neural and psychological mechanisms as memories resultant on conditioning to natural rewards (Robbins and Everitt 2002;Kelley 2004). For example, the acquisition of responding for cocaine-and sucrose-paired conditioned reinforcers is topographically similar, and both are equally persistent (Grimm et al. 2001(Grimm et al. , 2005Di Ciano and Everitt 2004). Therefore, we have employed an acquis...

Inhibition of β-Adrenergic Receptors Induces a Persistent Deficit in Retrieval of a Cocaine-Associated Memory Providing Protection against Reinstatement

“…ANOVA revealed a significant effect of chamber during the CPP trial (F 2,20 ¼ 18.58, po0.001), but post hoc analyses indicated that an equivalent amount of time was spent in the previously propranolol-and saline-paired chambers (p40.05). Thus, propranolol did not generate an affective state sufficient to induce a CPP or aversion, consistent with previous findings (Milton et al, 2008). We also evaluated the effects of propranolol on locomotor activity.…”

Limited efficacy of propranolol on the reconsolidation of fear memories

“…with either 10 mg/kg of propranolol or saline and tested again 48 h later (Test 2). This dosage of propranolol is one of the highest previously used in several studies to interfere with the consolidation or reconsolidation in several different types of memories, including both aversive and appetitive (e.g., Sara et al 1995;Przybyslawski et al 1999;Saber and Cain 2003;Debiec and LeDoux 2004;Diergaarde et al 2006;Abrari et al 2007;Milton et al 2008;Rodriguez-Romaguera et al 2009). All groups of rats had similar retention latencies at Test 1 and Test 2.…”

Compound Stimulus Presentation and the Norepinephrine Reuptake Inhibitor Atomoxetine Enhance Long-Term Extinction of Cocaine-Seeking Behavior

“…For example, LaLumiere et al (2010) found that repeated post-training administration of the b2-adrenergic agonist clenbuterol within the infralimbic cortex enhanced retention of extinction, as evidenced by lower responding in subsequent sessions. Other past work has found that interference with the NE system can disrupt stable memory formation as post-retrieval administration of propranolol can impair cocaine-conditioned place preference (Bernardi et al, 2006(Bernardi et al, , 2009Fricks-Gleason and Marshall, 2008) or conditioned reinforcement (Milton et al, 2008). These effects have been attributed to disrupted reconsolidation.…”