Dependence of mesolimbic dopamine transmission on Δ9-tetrahydrocannabinol

Tanda, Gianluigi; Loddo, P.; Chiara, G. Di

doi:10.1016/s0014-2999(99)00384-2

Cited by 83 publications

(45 citation statements)

References 10 publications

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“…Such a conclusion would also be consistent with results obtained using 6-hydroxydopamine lesions (30) and the consequent marked decrease in MSN spine density (31)(32)(33). It is also supported by previous data showing that morphine-withdrawn (34) and cannabis-dependent subjects (35) display a loss of dendritic spines paralleled by a reduced DAergic firing (36,37) and impaired DA release (38)(39)(40). Alternatively, and/or in addition to the previous interpretation, evidence for occlusion of LTD in ethanol-withdrawn rats can stem from the decreased spine density, shrinkage, and synaptic loss in this group of animals.…”

Section: Discussionsupporting

confidence: 88%

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: 88%

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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“…Although microdialysis studies have shown that cannabinoids increase dopamine over minutes (Chen et al, 1991;Tanda et al, 1997Tanda et al, , 1999, the temporal structure of this change is not known. Here we confirm that the potent CB 1 receptor agonist, WIN55,212-2, increases extracellular dopamine but reveal that this is manifested as an increase in the frequency and amplitude of rapid dopamine transients in the NAc.…”

Section: Discussionmentioning

confidence: 99%

Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats

Cheer¹,

Wassum²,

Heien³

et al. 2004

J. Neurosci.

309

244

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“…For example, there is evidence that chronic cannabinoid exposure alters the electrophysiological functions of rat (Hoffman et al, 2003) and mouse nucleus accumbens (Mato et al, 2005). Other studies have shown that in rats made tolerant to THC, administration of the cannabinoid antagonist rimonabant led to increased levels of corticotrophin-releasing factor in the central nucleus of the amygdala (Rodriguez de Fonseca et al, 1997), decreased levels of dopamine in the nucleus accumbens (Tanda et al, 1999), and decreased firing of dopaminergic cells in the ventral tegmental area (Diana et al, 1998). However, it should be noted that these studies were performed in vitro or used different regimens of THC exposure or different time frames to assess the consequences of THC exposure.…”

Section: Discussionmentioning

confidence: 99%

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol (THC) exposure, then allowing them to self-administer other drugs. In Experiment 1, THC preexposure did not alter the acquisition of cocaine self-administration or the amount of cocaine taken under a fixed-ratio 1 (FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine-seeking was significantly reduced in THC-exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive-ratio schedule, but it increased heroin self-administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC-exposed rats under FR1 heroin self-administration. When given cocaine, THCexposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC preexposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effectFwhich was verified in Experiment 3 using another model of anxiety, the light-dark testFmay explain the reduced reinforcing value of cocaine observed in THC-exposed rats in Experiment 1.

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Dependence of mesolimbic dopamine transmission on Δ9-tetrahydrocannabinol

Cited by 83 publications

References 10 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

Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

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