The basolateral amygdala and nucleus accumbens core mediate dissociable aspects of drug memory reconsolidation

A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of the nucleus accumbens core and the basolateral amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intranucleus accumbens core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the nucleus accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and nucleus accumbens core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.Through Pavlovian association with the effects of addictive drugs, a conditioned stimulus (CS) acquires both general motivational and sensory-specific conditioned reinforcing properties (Everitt et al. 2000). These associations contribute to the high likelihood of relapse in addicted individuals, yet the extinction of drug CSs by nonreinforced exposure has proved to be of limited therapeutic utility (Conklin and Tiffany 2002). In abstinent humans, drug CSs evoke salient and persistent memories of drug-taking experiences, inducing craving and relapse (Childress et al. 1988; O''Brien et al. 1992), while in animals they also precipitate relapse to, or reinstatement of, drug-seeking behavior (de Wit and Stewart 1981; Meil and See 1996; Fuchs et al. 1998; Weiss 2000). Thus, disrupting drug-related memories might significantly diminish relapse propensity on subsequent exposure to drug-paired CSs, and thereby promote abstinence.Exposure to a drug-associated CS also triggers a process of memory reconsolidation, which restabilizes the reactivated and labile memory (Nader 2003). While reconsolidation may adaptively update memories (Dudai 2006; Hupbach et al. 2007; Rossato et al. 2007; Lee 2009), its disruption may reduce the impact of intrusive or aberrant memories on behavior subsequently (Lee et al. 2005, 2006; Brunet et al. 2008; Kindt et al. 2009; Taubenfeld et al. 2009). The reconsolidation of CS–cocaine memories has been shown to depend upon protein synthesis and expression of the plasticity-associated immediate-early gene, zif268, in the basolateral amygdala (BLA), since zif268 knockdown at memory reactivation disrupted the acquired conditioned reinforcing properties of the CS measured in drug-seeking tasks days or weeks later (Lee et al. 2005, 2006).Although the BLA has an established role in CS-drug memory reconsolidation, it remains unclear whether other sites within limbic cortical-ventral striatal circuitry participate in this process. The nucleus accumbens core (AcbC) is a primary candidate, as zif268 is up-regulated in the AcbC as well as in the BLA following exposure to cocaine CSs (Thomas et al. 2003). Furthermore, the AcbC, which is strongly implicated in Pavlovian influences on drug seeking and relapse (Cardinal et al. 2002; Kalivas and McFarland 2003), has been shown to be a site where the reconsolidation of a drug conditioned place preference (CPP) memory can be disrupted (Miller and Marshall 2005).Given the evidence of increased zif268 expression in the AcbC following CS-drug memory reactivation, we investigated its requirement in the reconsolidation of cocaine-associated memories. To address this issue, we employed two different but complementary paradigms widely used to measure the conditioned effects of CSs associated with drugs of abuse: the acquisition of a new instrumental response with conditioned reinforcement (ANR) and CPP. These procedures have been used successfully to investigate the mechanisms underlying the reconsolidation of appetitive Pavlovian memories, but it is likely that they depend upon different associative mechanisms (Everitt et al. 1991; White and McDonald 1993) that in turn depend upon different neural loci within limbic cortical-striatal circuitry (Cardinal et al. 2002). Therefore, to enable a full comparison with the functional involvement of the BLA, we investigated the necessity for BLA zif268 expression in drug memory reconsolidation as assessed in the CPP paradigm.     

The development of counselling psychology in a clinical psychology service

This paper will describe one Clinical Psychology department's efforts to incorporate Counselling Psychology into the service. It is written from the experience of the Chartered Counselling Psychologist.     

Failure to replicate a QTL association between a DNA marker identified by EST00083 and IQ

In a paper published in this journal, a possible QTL association was reported between general cognitive ability and a marker, identified by an expressed sequence tag, EST00083 (Skuder et al., 1995). In two small samples, the frequency of the common allele of this DNA marker, which was shown to be in the threonine transfer RNA gene in mitochondrial DNA, was significantly greater in a high-IQ group than in a low-IQ group. As part of the ongoing IQ QTL Project (Plomin et al., 1995), we have attempted to replicate this QTL association. First, we found that the QTL association remained significant when we compared 51 high- and 51 -average IQ subjects, drawn in part from the samples used in the previous report. However, when we examined the association in new samples of 40 extremely high-IQ subjects and 50 average-IQ subjects, the association did not replicate. This underlies the need for replication in case-control studies of allelic association.     

The state and the market in Rawls

Studies in East European Thought - This essay attempts to interpret John Rawls's concept of the state in hisTheory of Justice. His concept is not an analysis of the existing monopoly capitalist...     

Beyond category sorting and pleasantness rating: Inducing relational and item-specific processing

In most studies of relational and item-specific processing, category sorting and pleasantness rating have been the main procedures used to induce these two types of processing. Because the two types of processing have been studied in a wide range of memory phenomena (Hunt & McDaniel, 1993), it is strange that other tasks have not been proposed and tested. The present experiment demonstrates that equivalent results can be obtained with three relational processing tasks (category sorting, narrative construction, and relational imagery) and equivalent results with three itemspecific processing tasks (pleasantness ratings, familiarity ratings, and single imagery).     

The role of regression and range effects in determination of the power function for electric shock

A scale for the apparent intensity of electric shock applied to the forearm was derived from cross-modality matching functions relating noise level, number, and force of handgrip to both line length and shock. For each response mode, the effects of psychophysical regression were estimated from the line judgments and used to make adjustments in the corresponding shock judgments. For shocks ranging from (1.0 to 5.5 mA, combined estimates of subjective magnitude were found to grow as the 2.26 power of the stimulating current.     

Self-Confrontation and Confrontation With Another as Determinants of Long-Term Value Change1

An experiment was carried out to determine whether attempts to change values would be less successful under conditions of confrontation with a significant other than under conditions of private self-confrontation. Rokeach's value change procedure was used to induce self-dissatisfaction in two experimcntal groups, one under anonymous conditions and the other under non-anonymous, face-to-face interaction with the experimenter. The rcsults confirm previously reported findings that significant long-term changes in values can be brought about by inducing feelings of self-dissatisfaction about contradictions within one's value-attitude system. The findings also showed that changes in equality and freedom 8 to 9 weeks after the experiment were equally great under both anonymous and non-anonymous conditions compared with a control condition. The results are discussed especially in relation to their practical implications for psychotherapy.     

Relative influence of prestige as a determiner of intelligence judgments for occupations

A forced-choice test was constructed to determine how well students could discriminate between occupations on the basis of the average intelligence of the members of the various occupational groups. At the outset, it was known that the prestige of the various occupations would have to be taken into account, and so the 72 forced-choice test items were systematically constructed to represent 24 combinations of intelligence and prestige differences. Accuracy at identifying the occupation with the higher average intelligence was significantly worse than chance, because subjects relied exclusively on prestige to make their choices. On items where the intelligence difference opposed the prestige difference, subjects could have improved their accuracy by flipping coins. The factors leading to significantly worse than chance accuracy, and the potency of prestige, are discussed.