Morphine withdrawal-induced morphological
changes in the nucleus accumbens
by
Spiga S, Puddu MC, Pisano M, Diana M.
Department of Animal Biology and Ecology,
University of Cagliari, Italy.
Eur J Neurosci. 2005 Nov;22(9):2332-40

ABSTRACT

Morphine withdrawal produces a hypofunction of mesencephalic dopamine neurons that impinge upon medium spiny neurons (MSN) of the forebrain. After chronic treatment (from 20 to 140 mg/kg of morphine twice a day over 14 days at escalating doses) rats were withdrawn from chronic morphine spontaneously and pharmacologically. In these two distinct conditions we studied the effects of withdrawal on the morphology of MSN of the core and shell of the nucleus accumbens (Nacc). MSN were stained with the Golgi-Cox procedure and analysed by a confocal laser-scanning microscope (CLSM). Our analysis shows that, shell and core MSN differed significantly for perikarya size and spine density, and the various morphine treatments did not affect the perikarya morphometry. Both spontaneous and naloxone-induced withdrawal produced a similar reduction in spine density in MS shell neurons, as compared with MS core neurons. This effect is selectively localized at the level of second order dendritic trunks where afferents converge. By contrast, spine density counts of accumbens MSN from rats chronically treated with morphine, did not reveal any change. Collectively, the results of the present study are twofold: (i) spontaneous and pharmacologically precipitated withdrawal, but not chronic morphine per se, affects spine density of target structures of a reduced mesolimbic dopamine transmission, and (ii) the reduction of spine density in second order dendritic trunks is selectively segregated in the MSN of the shell of the Nacc. In conclusion, morphine withdrawal dramatically alters spine density, selectively in second order dendritic trunks of Nacc shell MSN, thereby further impoverishing the already abated dopamine (DA) transmission. This is in line with recent views suggesting the hypodopaminergic state as a cardinal feature of opioid dependence.

Pain
Morphine
Tramadol
Oxycodone
Endomorphins
Novelty and pain
Fentanyl and ketamine
Signalling mechanisms
The extended amygdala
Opioids, mood and cognition
Tolerance, sensitization and dependence
Alpha-2 adrenergic agonists for opioid withdrawal
Medium spiny neurons in the nucleus accumbens and pleasure

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