New insights on neurobiological mechanisms underlying alcohol addiction

Cui, Changhai; Noronha, Antonio; Morikawa, Hitoshi; Alvarez, Veronica A.; Stuber, Garret D.; Szumlinski, Karen K.; Kash, Thomas L.; Roberto, Marisa; Wilcox, Mark V.

doi:10.1016/j.neuropharm.2012.09.022

Cited by 74 publications

(76 citation statements)

References 144 publications

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“…The PVN and the BNST are involved in stress, emotion, and ethanol responses (Armario, 2010;Cui et al, 2012;Koob, 2013), and we have previously shown that ethanol increases cellular 3a,5a-THP in these regions (Cook et al, 2014). Previous studies have shown that GABAergic neuroactive steroids contribute to negative feedback on the HPA axis at the level of the hypothalamus in rats (Owens et al, 1992;Patchev et al, 1996;Patchev et al, 1994), and activate the stress response in the hypothalamus of C57BL/6J mice (Sarkar et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Cook

Nelli

Neighbors

et al. 2014

Neuropsychopharmacol

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The neuroactive steroid (3a,5a)-3-hydroxypregnan-20-one (3a,5a-THP or allopregnanolone) is a positive modulator of GABA A receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic-pituitary-adrenal axis and elevates 3a,5a-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3a,5a-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3a,5a-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3a,5a-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3a,5a-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3a,5a-THP following ADX. In subcortical regions, 3a,5a-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3a,5a-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3a,5a-THP levels in several subcortical regions; however, the adrenal glands contribute to 3a,5a-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3a,5a-THP induction by ethanol is not due to a lack of colocalization of 3a,5a-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).

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Section: Discussionmentioning

confidence: 96%

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Cook

Nelli

Neighbors

et al. 2014

Neuropsychopharmacol

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“…128,189 Characterization of network changes via multiple modalities such as PET, fMRI, and diffusion tractography similarly elucidated possible sites for intervention in OCD. 43,109,182,212,226 Metabolic and functional imaging studies demonstrate network abnormalities in patients with Tourette syndrome (TS), 227 posttraumatic stress disorder (PTSD), 112 addiction, 46 and obesity. 71,153 Trials investigating the modulation of these targets with DBS for the treatment of psychiatric disease have followed.…”

Section: 54mentioning

confidence: 99%

Deep brain stimulation for psychiatric disorders: where we are now

Cleary

Ozpinar

Raslan

et al. 2015

FOC

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Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

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“…Thus, we examined GABAergic and glutamatergic synaptic transmission in the striatum, a brain region known to be affected by ethanol exposure and self-administration (Wang et al, 2010;Cuzon Carlson et al, 2011;Cui et al, 2013;Depoy et al, 2013;Fanelli et al, 2013). Electrophysiological analyses showed that inhibitory GABAergic synapses are depressed following the DID treatment in both striatal subregions, DLS and DMS.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic ethanol exposure affects brain pathways and neuronal circuits related to reward, stress (reviewed in Cui et al, 2013). Specifically, the dorsolateral (DLS) and dorsomedial striatum (DMS) are implicated in addiction (Koob and Volkow, 2010;Volkow et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, the dorsolateral (DLS) and dorsomedial striatum (DMS) are implicated in addiction (Koob and Volkow, 2010;Volkow et al, 2012). The dorsal striatum region is involved in ethanol drinking and it is the site of ethanol neuroadaptations (Wang et al, 2010;Cuzon Carlson et al, 2011;Cui et al, 2013;Depoy et al, 2013;Fanelli et al, 2013). Recently, we reported that non-human primates with 42 years of intermittent ethanol drinking exhibited a higher density of dendritic spines and altered putamen glutamatergic and GABAergic neurotransmission, a region homologous to the mouse DLS .…”

Section: Introductionmentioning

confidence: 99%

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Erratum: Repeated Binge-Like Ethanol Drinking Alters Ethanol Drinking Patterns and Depresses Striatal GABAergic Transmission

Wilcox¹,

Carlson²,

Sherazee³

et al. 2014

Neuropsychopharmacol

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Repeated cycles of binge alcohol drinking and abstinence are key components in the development of dependence. However, the precise behavioral mechanisms underlying binge-like drinking and its consequences on striatal synaptic physiology remain unclear. In the present study, ethanol and water drinking patterns were recorded with high temporal resolution over 6 weeks of binge-like ethanol drinking using the 'drinking in the dark' (DID) protocol. The bottle exchange occurring at the beginning of each session prompted a transient increase in the drinking rate that might facilitate the acquisition of ethanol binge-like drinking. Ethanol drinking mice also displayed a 'front-loading' behavior, in which the highest rate of drinking was recorded during the first 15 min. This rate increased over weeks and paralleled the mild escalation of blood ethanol concentrations. GABAergic and glutamatergic transmission in the dorsal striatum were examined following DID. Spontaneous glutamatergic transmission and the density of dendritic spines were unchanged after ethanol drinking. However, the frequency of GABA A receptor-mediated inhibitory postsynaptic currents was depressed in medium spiny neurons of ethanol drinking mice. A history of ethanol drinking also increased ethanol preference and altered the acute ethanol effects on GABAergic transmission differentially in dorsolateral and dorsomedial striatum. Together, the study shows that the bottle exchange during DID promotes fast, voluntary ethanol drinking and that this intermittent pattern of ethanol drinking causes a depression of GABAergic transmission in the dorsal striatum.

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New insights on neurobiological mechanisms underlying alcohol addiction

Cited by 74 publications

References 144 publications

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

Deep brain stimulation for psychiatric disorders: where we are now

Erratum: Repeated Binge-Like Ethanol Drinking Alters Ethanol Drinking Patterns and Depresses Striatal GABAergic Transmission

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