Morphine withdrawal‐induced morphological changes in the nucleus accumbens

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 After chronic treatment (from 20 to 140 mg/kg of morphine twice a day over 14 days at escalating doses) rats were withdrawn from chronic morphine spontaneously and pharmacologically.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.

Orexin Mediates the Expression of Precipitated Morphine Withdrawal and Concurrent Activation of the Nucleus Accumbens Shell

“…Furthermore, in response to morphine withdrawal, there is a reduction in spine density that is specific to the dendrites of medium spiny neurons located in the AcbSh. This reduction correlates with the severity of somatic symptoms of morphine withdrawal (52). Here, we also demonstrate that Acb neurons respond to naloxone-induced morphine withdrawal, a finding consistent with the literature, and suggest a role for orexin in this response.…”

A half century of experimental neuroanatomical tracing

“…Modeling of 3D reconstructions of Golgi-Cox impregnated material via confocal microscopic imaging has recently been introduced as the so-called ‗reflection method' (Spiga et al, 2005). This procedure has some advantages over conventional optical microscopy, particularly the rejection of out-of-focus light.…”

Neonatal Abstinence Syndrome

“…The ventral tegmental area of the midbrain, the storage center of dopamine, releases decreased dopamine during opioid withdrawal. 80,81 Opioid withdrawal also causes decreased serotonin expression in the dorsal raphe nucleus, 82,83 causing sleep disturbances in neonates undergoing opioid withdrawal. Opioid deficits also affect the functioning of the autonomic and peripheral nervous systems, as well as the gastrointestinal system.…”