Mechanisms of Psychostimulant-Induced Structural Plasticity

Golden, Sam A.; Russo, Scott J.

doi:10.1101/cshperspect.a011957

Cited by 52 publications

(37 citation statements)

References 171 publications

(173 reference statements)

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“…Moreover, activation of CB1Rs in the NAc locally disinhibits dopamine release in this region (Cheer et al, 2004; Chen et al, 1993; Sperlágh et al, 2009) as does estradiol in the female NAc and caudate resulting in increased locomotor responses to psychostimulants (Becker and Rudick, 1999; Schultz et al, 2009; Thompson and Moss, 1994). Sustained enhancement of dopamine neurotransmission in the NAc and changes in MSN excitability are recognized as a key factors to the onset of drug addiction through structural remodeling of reward circuits leading to enhanced behavioral responses to psychostimulants (Golden and Russo, 2012; Kalivas and Duffy, 1990; Kourrich and Thomas, 2009). …”

Section: Discussionmentioning

confidence: 99%

“…Although initial studies indicated that repeated exposure to psychostimulants increased dendritic spine density within the NAc core (e.g., Li et al, 2004; Norrholm et al, 2003), more recent studies using advanced staining techniques and 3-D imaging, thought to more accurately represent neuroanatomical structure (Golden and Russo, 2012), have observed a decrease in spine density within this brain region following repeated cocaine administration (Dumitriu et al, 2012; Waselus et al, 2013). Independent of methodological issues, dendritic spine plasticity of MSNs in the NAc are associated with enhanced behavioral responsiveness to psychostimulants.…”

Section: Discussionmentioning

confidence: 99%

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Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine

et al. 2016

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Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction. The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glutamate receptor type 5 (mGluR5). However, the downstream effectors of this ER/mGluR5 signaling pathway are unknown. Here we investigate whether cannabinoid 1 receptor (CB1R) activation is a part of the mechanism whereby estradiol influences behavioral and synaptic correlates of addiction. Following repeated cocaine administration, estradiol-treated ovariectomized rats exhibited both sensitized locomotor responses and decreases in the dendritic spine density of nucleus accumbens core medium-spiny neurons in comparison to oil-treated controls. Both effects of estradiol were blocked by AM251, a CB1R inverse agonist. These results indicate that part of the signaling mechanism through which estradiol impacts behavioral and synaptic correlates of addiction in female rats requires activation of CB1Rs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine

et al. 2016

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“…In contrast, the effect of psychostimulants on dendritic spines has been the focus of numerous studies(Golden and Russo 2012). The results of these studies suggest that patterns of dendritic spine plasticity depend on a number of factors, including route and context of drug administration, drug administration regime, and length of withdrawal after drug cessation (Golden and Russo 2012). However, what is particularly intriguing is that dendritic spine density in the NAc core is decreased 24 hours after repeated psychostimulant exposure (Dumitrui et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5

2014

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Accumulating evidence from human and rodent studies suggests that females are more sensitive to the motivating and rewarding properties of drugs of abuse. Numerous reports implicate estradiol in enhancing drug-related responses in females, yet the neurobiological mechanisms underlying this effect of estradiol are unknown. Because dendritic spine plasticity in the nucleus accumbens (NAc) is linked to the addictive effects of drugs, we examined the influence of estradiol on dendritic spines in this region. Previously our lab demonstrated that in female medium spiny neurons estradiol activates metabotropic glutamate receptor subtype five (mGluR5), a G-protein coupled receptor already implicated in the etiology of drug addiction. Thus we sought to determine whether mGluR5 is a part of the mechanism by which estradiol affects dendritic spine density in the NAc. To test this hypothesis, ovariectomized female rats were treated with the mGluR5 antagonist, MPEP, or vehicle prior to estradiol (or oil) treatment and 24hrs later dendritic spine density was evaluated by DiI labeling and confocal microscopy. We found that estradiol decreased dendritic spine density in the NAc core, and that pretreatment with MPEP blocked this effect. In contrast, MPEP had no effect on dendritic spine density in the NAc shell or CA1 region of the hippocampus, two regions in which estradiol increased the density of dendritic spines. As dendritic spine plasticity in the NAc core has behavioral consequences for drug addiction, these data provide a clue as to how estradiol acts in females to enhance behavioral responses to drugs of abuse.

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“…To confirm the specificity of the proteolytic response, we then used the pharmacologic inhibitor tPA serpin (Serpini1) (Galliciotti and Sonderegger, 2006). The elevated tPA activity in adult Lynx1 KO mice with MD was significantly decreased with tPA serpin in ex vivo V1 homogenates (Lynx1 KO MD, n ϭ 4; 0.61 Ϯ 0.079 vs Lynx1 KO ϩ tPA Serpin, n ϭ 4; 0.49 Ϯ 0.076, p Ͻ 0.05, paired Student's t test; Figure 1B).…”

Section: Tpa Activity Elevates In Adult V1 Following MD In Lynx1 Ko Micementioning

confidence: 99%

Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1

et al. 2015

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Experience-dependent cortical plasticity declines with age. At the molecular level, experience-dependent proteolytic activity of tissue plasminogen activator (tPA) becomes restricted in the adult brain if mice are raised in standard cages. Understanding the mechanism for the loss of permissive proteolytic activity is therefore a key link for improving function in adult brains. Using the mouse primary visual cortex (V1) as a model, we demonstrate that tPA activity in V1 can be unmasked following 4 d of monocular deprivation when the mice older than 2 months are raised in standard cages by the genetic removal of Lynx1, a negative regulator of adult plasticity. This was also associated with the reduction of stubby and thin spine density and enhancement of ocular dominance shift in adult V1 of Lynx1 knock-out (KO) mice. These structural and functional changes were tPA-dependent because genetic removal of tPA in Lynx1 KO mice can block the monocular deprivation-dependent reduction of dendritic spine density, whereas both genetic and adult specific inhibition of tPA activity can ablate the ocular dominance shift in Lynx1 KO mice. Our work demonstrates that the adult brain has an intrinsic potential for experience-dependent elevation of proteolytic activity to express juvenile-like structural and functional changes but is effectively limited by Lynx1 if mice are raised in standard cages. Insights into the Lynx1-tPA plasticity mechanism may provide novel therapeutic targets for adult brain disorders.

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Mechanisms of Psychostimulant-Induced Structural Plasticity

Cited by 52 publications

References 171 publications

Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine

Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine

Estradiol mediates dendritic spine plasticity in the nucleus accumbens core through activation of mGluR5

Unmasking Proteolytic Activity for Adult Visual Cortex Plasticity by the Removal of Lynx1

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