Post-retrieval disruption of a cocaine conditioned place preference by systemic and intrabasolateral amygdala β2- and α1-adrenergic antagonists

Previous work has demonstrated post-retrieval impairment in associative learning paradigms, including those mediated by drugs of abuse, using nonspecific β-adrenergic receptor (β-AR) antagonists. Remarkably little is known about the role of the specific β-AR subtypes, or other adrenergic receptors, in these effects. The current study examined the effects of β₁ and β₂, as well as α₁-adrenergic receptor antagonism following retrieval of a cocaine conditioned place preference (CPP). We found that rats administered the β₂ antagonist ICI 118,551 (8 mg/kg intraperitoneal [IP]) or the α₁ antagonist prazosin (1 mg/kg IP) following a drug-free test for CPP showed attenuated preference during a subsequent test, while the β₁ antagonist betaxolol (5 or 10 mg/kg IP) and a lower dose of prazosin (0.3 mg/kg IP) had no effect. Furthermore, post-test microinfusion of ICI 118,551 (6 nmol/side) or prazosin (0.5 nmol/side) into the basolateral amygdala (BLA) also impaired a subsequent preference. Systemic or intra-BLA ICI 118,551 or prazosin administered to rats in their home cages, in the absence of a preference test, had no effect on CPP 24 h later. ICI 118,551 also attenuated the FOS response in the BLA induced by the CPP test. These results are the first to demonstrate a role for α₁- and β₂-specific adrenergic mechanisms in post-retrieval memory processes. These systemic and site-specific injections, as well as the FOS immunohistochemical analyses, implicate the importance of specific noradrenergic signaling mechanisms within the BLA in post-retrieval plasticity.Substantial evidence indicates that information acquired during a learning event is initially plastic, at which time memory retention can be disrupted, but is strengthened by a time-dependent consolidation process (McGaugh 2000). Recent work has focused on retrieval-induced plasticity, a process by which changes in the retention of previously acquired information are possible. The notion of reconsolidation, one theoretical mechanism by which such changes may occur, suggests that a retrieved memory enters a labile state and is vulnerable to disruption (Sara 2000; Nader 2003). Although the theoretical mechanisms underlying reconsolidation remain unclear, the behavioral effects have been demonstrated across many different learning paradigms using a variety of pharmacological manipulations (for review, see Tronson and Taylor 2007; Diergaarde et al. 2008). Studies with aversive and appetitive preparations, including drug reward-mediated learning, have demonstrated that the noradrenergic system is important for these post-retrieval memory processes (Przybyslawski et al. 1999; Debiec and Ledoux 2004; Bernardi et al. 2006; Diergaarde et al. 2006; Robinson and Franklin 2007; Abrari et al. 2008; Fricks-Gleason and Marshall 2008; Milton et al. 2008). For example, using an animal model of cocaine-conditioned behaviors, Bernardi et al. (2006) demonstrated that systemic post-retrieval administration of propranolol impaired a subsequent conditioned place preference (CPP), suggesting that β-adrenergic receptors (β-ARs) play an important role in processes occurring following drug memory retrieval.However, most of what is known about the noradrenergic system in the memory processes that follow cued reminder trials comes from studies that use nonspecific β-AR antagonists, such as propranolol. As a consequence, several issues regarding ARs and post-retrieval memory processes remain unresolved. First, because propranolol has affinity for both β₁- and β₂-AR subtypes, it is unclear which subtype mediates these effects. To date, no studies have examined reconsolidation-like impairments using subtype-specific β-AR antagonists, which is important because more specific medications may be equally efficacious with less adverse effects. Second, no studies to date have examined α-ARs regarding a potential role in reconsolidation-like effects. α-ARs—specifically α₁-ARs—have a demonstrated role in memory consolidation (Ferry et al. 1999a,b) and may also mediate post-retrieval processes. Third, although the BLA has had a demonstrated role in reconsolidation-like effects in numerous studies, the behavioral conditions during retrieval of drug-associated memories leading to gene expression within the basolateral amygdala (BLA) have not clearly been defined. Specifically, in the CPP paradigm used here, it is unclear whether exposure to a cocaine cue alone will induce gene expression or whether a preference for the drug-associated environment needs to be expressed for BLA involvement (Franklin and Druhan 2000; Miller and Marshall 2005).Understanding the role of specific adrenergic receptors in mediating post-retrieval memory processes is particularly important in drug-induced CPP. In humans, drug-associated stimuli can facilitate drug use (Gawin 1991; See 2005) or precipitate relapse following abstinence (O''Brien et al. 1992). Thus, pharmacotherapies targeting these memory processes would benefit from a clearer understanding of the specific receptors that mediate behavioral effects (Taylor et al. 2009).Here, we first examined the effects of systemic post-test β₁-, β₂-, and α₁-AR antagonism on cocaine CPP. We then focused on the BLA due to its involvement in reconsolidation-like effects in drug learning paradigms (e.g., Lee et al. 2005), employing microinfusions of AR antagonists and measuring FOS immunoreactivity (FOS-IR) to examine the BLA as a potential site of AR-mediated impairments.     

Improving left spatial neglect through music scale playing

The study assessed whether the auditory reference provided by a music scale could improve spatial exploration of a standard musical instrument keyboard in right‐brain‐damaged patients with left spatial neglect. As performing music scales involves the production of predictable successive pitches, the expectation of the subsequent note may facilitate patients to explore a larger extension of space in the left affected side, during the production of music scales from right to left. Eleven right‐brain‐damaged stroke patients with left spatial neglect, 12 patients without neglect, and 12 age‐matched healthy participants played descending scales on a music keyboard. In a counterbalanced design, the participants' exploratory performance was assessed while producing scales in three feedback conditions: With congruent sound, no‐sound, or random sound feedback provided by the keyboard. The number of keys played and the timing of key press were recorded. Spatial exploration by patients with left neglect was superior with congruent sound feedback, compared to both Silence and Random sound conditions. Both the congruent and incongruent sound conditions were associated with a greater deceleration in all groups. The frame provided by the music scale improves exploration of the left side of space, contralateral to the right hemisphere, damaged in patients with left neglect. Performing a scale with congruent sounds may trigger at some extent preserved auditory and spatial multisensory representations of successive sounds, thus influencing the time course of space scanning, and ultimately resulting in a more extensive spatial exploration. These findings offer new perspectives also for the rehabilitation of the disorder.     

Alone at the playground

Starting pre-school is a major stepping stone for children’s peer relations. Yet, some children spend their recess time alone, albeit in the presence of playful peers. These solitary behaviours have been noted in the literature as an alarm signal for a maladaptive social development. In this study, we identified four kinds of non-social behaviours engaged at recess (reticent, solitary-pretend, -functional, and -passive); and we examined the extent to which these different behaviours were related to social solitude at the playground six months later. Therefore, 97 children (aged 4–6 years old) were observed at the playground and their social-emotional skills were tested. Solitude was assessed through an innovative measuring method, based on Radio Frequency Identification Devices. The results demonstrated that solitary-pretend play in girls was related to an increase in solitary behaviours later on. Nevertheless, children who engaged in non-social behaviours showed a general lack of emotional skills, which may explain their initial withdrawal.     

Vulnerability Across the Life Course

This issue defines vulnerability as a key interdisciplinary concept for understanding life trajectories. Moreover, it develops a life course framework to study vulnerability along three structuring axes of research: multidimensionality, multilevel, and multidirectionality.     

Assessing short summaries with human judgments procedure and latent semantic analysis in narrative and expository texts

In the present study, we tested a computer-based procedure for assessing very concise summaries (50 words long) of two types of text (narrative and expository) using latent semantic analysis (LSA) in comparison with the judgments of four human experts. LSA was used to estimate semantic similarity using six different methods: four holistic (summary-text, summary-summaries, summary-expert summaries, and pregraded-ungraded summary) and two componential (summary-sentence text and summary-main sentence text). A total of 390 Spanish middle and high school students (14–16 years old) and six experts read a narrative or expository text and later summarized it. The results support the viability of developing a computerized assessment tool using human judgments and LSA, although the correlation between human judgments and LSA was higher in the narrative text than in the expository, and LSA correlated more with human content ratings than with human coherence ratings. Finally, the holistic methods were found to be more reliable than the componential methods analyzed in this study.     

Contents to Volume 5

Volume Contents

Contents to Volume 5