Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner

Abstract

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.addiction | reconsolidation | hippocampus morphine

Impact of chronic morphine on delta opioid receptor-expressing neurons in the mouse hippocampus

“…This is in line with the strong increase in theta rhythm observed in mice chronically treated with morphine (Liu et al, 2010). Theta oscillations occur during spatial navigation, learning and memory formation (Jinno and Kosaka, 2002, Klausberger and Somogyi, 2008, Klausberger, 2009, Somogyi and Klausberger, 2005) and previous reports indicated spatial memory impairment in heroin abusers (Ornstein et al, 2000) as well as in morphine-dependent rats (Zhang et al, 2005, Marinelli et al, 2007, Hu et al, 2010, Taubenfeld et al, 2010) and mice (Lu et al, 2010). It also supports a role for DOP receptors in drug-context associations (Ciccocioppo et al, 2002, Marinelli et al, 2009, Le Merrer et al, 2011, Faget et al, 2012, Le Merrer et al, 2012b).…”

Extinction after retrieval: Effects on the associative and nonassociative components of remote contextual fear memory

“…This would mean that the retrieval of fear memory triggered by the mere re-exposure to the conditioning context (i.e., in the absence of US) might only be able to reactivate the fear experience partially when stable remote memories are involved (Frankland et al 2006). It is important to note that the latter cannot be considered a general rule, since a need for US presentation during reactivation has been observed when appetitive reconsolidation is involved (Lee and Everitt 2008;Taubenfeld et al 2010). However, it has also to be considered that US presentation during retrieval is not always applicable, especially when aversive fear memories, like those characterizing PTSD, are considered.…”

Consequences at adulthood of transient inactivation of the parahippocampal and prefrontal regions during early development: new insights from a disconnection animal model for schizophrenia

“…CPP may be supported by context-reward associations, but the contribution of discrete cue-reward associations cannot be discounted (Ito et al, 2008). The disruption of memory reconsolidation in CPP paradigms can be achieved by hippocampal-targeted treatments (Sakurai et al, 2007; Taubenfeld et al, 2010) and intra-BLA protein synthesis inhibition (Milekic et al, 2006) suggesting that context-reward memories do undergo reconsolidation.…”