anisomycin and Morphine-Dependence

Positive and negative emotional experiences induced by addictive drugs play an important role in the development of dysfunctional drug-related memory, which becomes resistant to extinction and contributes to high rate of relapse. Those memories may undergo a process called reconsolidation that in some cases can be disrupted by pharmacological treatment. The basolateral amygdala (BLA) has been shown to mediate the reconsolidation of drug-related appetitive memory, but its role in withdrawal-related aversive memory remains elusive. The present study used conditioned place preference (CPP) and conditioned place aversion (CPA) paradigms to investigate the role of BLA and its noradrenergic receptors in reconsolidation of morphine-associated emotional memory in rats. We found that inhibition of protein synthesis in BLA disrupted the reconsolidation of morphine CPP (m-CPP) and CPA related to morphine withdrawal (m-CPA). A high dose of the β-noradrenergic receptor antagonist propranolol (3 µg) in BLA-impaired reconsolidation of m-CPA but not m-CPP, whereas a low dose (0.3 µg) was ineffective. In contrast, neither low nor high doses of the α-noradrenergic receptor antagonist phentolamine (1 or 10 µg) blocked the reconsolidation of m-CPP and m-CPA. In addition, infusion of propranolol (3 µg) into nucleus accumbens after retrieval of either m-CPP or m-CPA did not affect its reconsolidation. The findings indicate that appetitive and aversive addictive memories share common neural substrates in BLA, but the specific neurotransmitter mechanism on reconsolidation of morphine-associated negative and positive memories can be dissociable.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Amygdala; Analysis of Variance; Animals; Anisomycin; Appetitive Behavior; Avoidance Learning; Choice Behavior; Conditioning, Psychological; Dose-Response Relationship, Drug; Male; Memory; Microinjections; Morphine; Morphine Dependence; Narcotics; Nucleus Accumbens; Phentolamine; Propranolol; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta; Recurrence; Substance Withdrawal Syndrome

In human addicts, craving and relapse are frequently evoked by the recall of memories connected to a drug experience. Established memories can become labile if recalled and can then be disrupted by several interfering events and pharmacological treatments, including inhibition of protein synthesis. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to pathological states. Here, we tested whether the memory of a drug experience can be weakened by inhibiting protein synthesis after the reactivation of its trace. We found that an established morphine conditioned place preference (mCPP) was persistently disrupted if protein synthesis was blocked by either anisomycin or cycloheximide after the representation of a conditioning session. Unlike other types of memories, an established mCPP did not become labile after contextual recall, but required the concomitant re-experience of both the conditioning context and the drug. An established mCPP was disrupted after the conditioning session if protein synthesis was blocked selectively in the hippocampus, basolateral amygdala, or nucleus accumbens but not in the ventral tegmental area. This disruption seems to be permanent, because the preference did not return after further conditioning. Thus, established memories induced by a drug of abuse can be persistently disrupted after reactivation of the conditioning experience.

Topics: Amnesia, Retrograde; Amygdala; Animals; Anisomycin; Association Learning; Conditioning, Classical; Cues; Cycloheximide; Hippocampus; Learning; Male; Mental Recall; Microinjections; Morphine; Morphine Dependence; Nerve Tissue Proteins; Nucleus Accumbens; Organ Specificity; Protein Synthesis Inhibitors; Rats; Rats, Long-Evans; Reward; Spatial Behavior; Time Factors; Ventral Tegmental Area