PMID:23775491

Citation	Sun, L, Hu, L, Li, Y and Cui, C (2014) Mesoaccumbens dopamine signaling alteration underlies behavioral transition from tolerance to sensitization to morphine rewarding properties during morphine withdrawal. Brain Struct Funct 219:1755-71
Abstract	Although the firing activity of dopamine (DA) neurons in the ventral tegmental area (VTA) and the behavioral response to morphine rewarding properties alter as opiate withdrawal, little is known about the dynamic changes in DA signal pathway from the VTA to the nucleus accumbens (NAc) during prolonged withdrawal, and whether the changes are indicative of vulnerability to relapse of drug abuse. Here we report that morphine spontaneously withdrawn (SW) rats are incapable of responding to small dose of morphine-induced conditioned place preference (CPP) from 24h-SW to 30d-SW, but recover response at 45d-SW. Interestingly, mesoaccumbens DA signaling, including the firing of DA neurons in the VTA, contents of DA and its metabolic ratio, and the membrane level of dopamine D1 receptor in the NAc elicited by morphine challenge, display a similar pattern of time-dependent changes during morphine withdrawal. Moreover, blockade of D1 receptor abolishes this behavioral transition. In addition, a strong correlation was found between % change in CPP score and membrane D1 receptor level induced by morphine challenge. These results indicate a time-dependent behavioral switch from tolerance to sensitization during the prolonged withdrawal, which could offer a window for therapeutic intervention via manipulations of D1 receptors.
Links	PubMed Online version:10.1007/s00429-013-0599-2
Keywords	Action Potentials/drug effects; Analgesics, Opioid/adverse effects; Animals; Apomorphine/pharmacology; Conditioning, Operant/drug effects; Disease Models, Animal; Dopamine/metabolism; Dopamine Agents/pharmacology; Dopaminergic Neurons/drug effects; Dopaminergic Neurons/physiology; Male; Morphine/adverse effects; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1/metabolism; Reward; Signal Transduction/drug effects; Signal Transduction/physiology; Substance Withdrawal Syndrome/physiopathology; Time Factors; Ventral Tegmental Area/metabolism; Ventral Tegmental Area/pathology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:DRD1	involved_in	GO:0043278: response to morphine	ECO:0000270: expression pattern evidence used in manual assertion		P		Seeded From UniProt	complete

References

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