Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat

Rothblat, David S.; Rubin, Emmanuel; Schneider, Jay S.

doi:10.1016/s0304-3940(01)01548-8

Cited by 46 publications

(32 citation statements)

References 19 publications

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“…Thus, THcontaining terminals appear to be present unmodified, but TH quantity, and presumably DA synthesis, is reduced in EtOH-W. Although we did not measure other indices of DA signaling in the present work, such changes are consistent with previous reports (20), and further add to the idea of a reduction in DAergic firing and DA microdialysates observed in the Nacc of rats suspended from chronic ethanol administration (29). In addition, PSD-95 immunoreactivity and spine density are similarly reduced in ethanol-withdrawn rats, compared with animals that were tested while still intoxicated, thereby suggesting, as a whole, yet another example of aberrant structural synaptic plasticity that takes place in association with ethanol withdrawal, a crucial phase of ethanol dependence.…”

Section: Discussionsupporting

confidence: 91%

“…In addition, reduced expression of tyrosine hydroxylase (TH) has been demonstrated in the ventral striatum of rats maintained on a chronic ethanol-containing diet (20), and a decrease of neurofilament protein immunoreactivity in the VTA (21) has been reported. Thus, in the present work, we sought to investigate possible alterations produced by ethanol withdrawal on mesocorticolimbic transmission by exploring critical elements whose presence is strictly correlated with DAergic and GLUergic function, respectively: TH-and dopamine transporter (DAT)-positive fibers and postsynaptic density 95 (PSD-95).…”

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confidence: 99%

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Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Spiga

Talani

Mulas

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.A lcohol addiction is a major public health problem in the Western world. In the United States alone, about 15% of adults have an alcohol-related disorder at some point in their life, and alcohol abuse costs the economy over $220 billion per y in medical care and productivity loss (1). A general consensus has emerged on drug addiction as a substance-induced, aberrant form of neural plasticity (2, 3). The nucleus accumbens (Nacc) plays a central role in the neural circuits that are responsible for goal-directed behaviors (4, 5) and in addictive states. Its activity is heavily modulated by glutamate-(GLU) and dopamine-(DA) containing projections that originate in cortical and limbic regions and converge on a common postsynaptic target: the medium spiny neuron (MSN). Furthermore, DA modulates GLU inputs to Nacc neurons (6, 7), both by directly influencing synaptic transmission and by modulating voltage-dependent conductances (8). Accordingly, interactions between DA and GLU are involved in druginduced locomotor stimulation and addiction (9, 10) and may represent useful potential therapeutic targets (11,12). In the distal portion of the dendrites of MSNs a significant subpopulation of spines shows a particular synaptic architecture, called the "striatal microcircuit" or "synaptic triad" (13, 14), which is characterized by a double, discrete, and reciprocal interaction between DA and GLU aff...

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Spiga

Talani

Mulas

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In another study, 1 year of alcohol ingestion increased DA transporter (DAT) protein levels (by 60%) in both the dorsal and ventral striatum of Sprague-Dawley rats (Rothblat et al 2001). The acceleration in DA uptake, observed in both the nonhuman primate model and in the rat after chronic alcohol vapor inhalation (current study), is also consistent with recent findings, which documented an increase in DAT sites in the rat brain after 24 days of alcohol consumption (Jiao et al 2006).…”

Section: Discussionsupporting

confidence: 89%

Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen

et al. 2007

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“…binding in the striatum Simantov, 1993 , while the dopamine transporter was increased in both the dorsal and ventral striatum, in rats treated for 1 year Ž . with ethanol Rothblat et al, 2001 . In addition, there were no changes in dopamine transport subse-Ž quent to chronic administration of pentobarbital a .…”

Section: Discussionmentioning

confidence: 99%

Kappa opioid agonists alter dopamine markers and cocaine-stimulated locomotor activity

Collins

D’Addario

et al. 2001

Behavioral Pharmacology

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To better understand the influence of kappa-opioid agonists on the effects of cocaine, rats were treated with daily injections of the selective kappa-opioid agonist U-69593 or bremazocine. In combination with 10 mg/kg cocaine, both compounds, at a dose of 0.32 mg/kg, greatly diminished locomotor activity, and these effects were maintained over a period of 5 days. In addition, the response to a challenge injection of 10 mg/kg cocaine several days after the end of kappa-Opioid agonist treatment with or without cocaine was markedly reduced. When naltrexone was given in combination with U-69593, it blocked the reduction in cocaine-induced locomotor activity after U-69593 treatment alone. However, a single injection of either kappa-opioid agonist alone had no effect on cocaine-induced locomotion several days later (i.e. no long-term effects), suggesting that multiple injections of the kappa-opioid agonist are needed to reduce the locomotor activating effects of cocaine other than acutely. In addition, treatment with the kappa-opioid agonist U-69593 (0.32 mg/kg) over a 5-day period decreased dopamine transporter densities in the caudate putamen, and this was also blocked by co-administration of naltrexone.

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Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat

Cited by 46 publications

References 19 publications

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen

Kappa opioid agonists alter dopamine markers and cocaine-stimulated locomotor activity

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