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Persistent and reversible morphine withdrawal-induced morphological changes in the nucleus accumbens
Marco Diana1, Saturnino Spiga, Elio Acquas
1Department of Drug Sciences University of Sassari, Via Muroni n. 23, 07100 Sassari, Italy. dsfdiana@uniss.it
Annals of the New York Academy of Sciences
|November 16, 2006
Summary
Morphine withdrawal significantly reduces spine density in nucleus accumbens shell neurons, impacting dopamine transmission. This lasting but reversible change may explain addiction
Area of Science:
- Neuroscience
- Neurobiology
- Addiction Research
Background:
- Chronic morphine use alters dopamine (DA) system function.
- Mesolimbic DA hypofunction is a hallmark of drug dependence.
- Nucleus accumbens (NAcc) medium spiny neurons (MSN) are critical in reward pathways.
Purpose of the Study:
- To investigate the effects of morphine withdrawal on MSN spine density in the NAcc.
- To differentiate withdrawal-induced changes from chronic morphine effects.
- To determine the temporal and regional specificity of these structural alterations.
Main Methods:
- Rats underwent chronic morphine treatment followed by spontaneous or naloxone-induced withdrawal.
- Golgi-Cox staining was used to visualize neuronal morphology.
- Confocal laser-scanning microscopy analyzed spine density on NAcc MSN (core and shell).
Main Results:
- Both spontaneous and naloxone-induced withdrawal caused a long-lasting, reversible reduction in spine density on NAcc shell MSN.
- This reduction was specific to second-order dendritic trunks and persisted up to 14 days post-withdrawal.
- Chronic morphine treatment alone did not alter spine density over time.
- NAcc core MSN spine density remained unaffected by withdrawal.
Conclusions:
- Morphine withdrawal, not chronic morphine use, persistently reduces MSN spine density in the NAcc shell.
- This structural change occurs under conditions of reduced mesolimbic DA transmission.
- The findings suggest a link between withdrawal-induced spine loss and addiction consequences like craving and loss of control.
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