Association of galanin haplotypes with alcoholism and anxiety in two ethnically distinct populations

Belfer, Inna; Hipp, Heather S.; McKnight, Crystal; Evans, Catherine; Búzás, Beáta; Bollettino, A.; Albaugh, Bernard; Virkkunen, Matti; Yuan, Qiaoping; Max, Mitchell B.; Goldman, David; Enoch, Mary‐Anne

doi:10.1038/sj.mp.4001768

Cited by 73 publications

(90 citation statements)

References 44 publications

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“…Further, the levels of GAL mRNA in the PVN were positively correlated with the amount of ethanol consumed. These findings confirm our earlier report on GAL (Leibowitz et al, 2003) and are substantiated by a recent report demonstrating an association of GAL haplotypes with alcoholism in distinct populations (Belfer et al, 2006).…”

Section: Effect Of Ethanol On Gal In the Pvnsupporting

confidence: 82%

Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating Triglycerides

Chang

Karatayev

Ahsan

et al. 2007

Alcoholism Clin & Exp Res

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Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN).Method: Adult, male Sprague-Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured.Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN.Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol.

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Section: Effect Of Ethanol On Gal In the Pvnsupporting

confidence: 82%

Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating Triglycerides

Chang

Karatayev

Ahsan

et al. 2007

Alcoholism Clin & Exp Res

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“…A link between galanin and abnormal levels of alcohol craving or elevated consumption is suggested by a reported association of galanin and GAL 3 with alcoholism. Galanin haplotypes and increased alcoholism risk were identified in two distinct populations (Belfer et al, 2006), whereas there was no effect of GAL 1 or GAL 2 haplotypes on alcoholism risk (see section VII).…”

Section: Galanin Family Peptides and Receptorsmentioning

confidence: 99%

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

et al. 2014

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“…Thus, galanin interacts with 5-HT1A receptors, and galanin antagonists and agonists have anxiolytic and antidepressive effects in animal experiments (144)(145)(146)(147)(148)(149)(150)(151). Interestingly, association of genes encoding galanin and/or GalR3 has been reported for psychiatric phenotypes (152)(153)(154), including panic disorder (155), depression-related parameters (156)(157)(158), and nicotine dependence (159,160).…”

Section: Significancementioning

confidence: 99%

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

Maître

Barde

Palkovits

et al. 2013

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

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Using riboprobe in situ hybridization, we studied the localization of the transcripts for the neuropeptide galanin and its receptors (GalR1-R3), tryptophan hydroxylase 2, tyrosine hydroxylase, and nitric oxide synthase as well as the three vesicular glutamate transporters (VGLUT 1-3) in the locus coeruleus (LC) and the dorsal raphe nucleus (DRN) regions of postmortem human brains. Quantitative real-time PCR (qPCR) was used also. Galanin and GalR3 mRNA were found in many noradrenergic LC neurons, and GalR3 overlapped with serotonin neurons in the DRN. The qPCR analysis at the LC level ranked the transcripts in the following order in the LC: galanin >> GalR3 >> GalR1 > GalR2; in the DRN the ranking was galanin >> GalR3 >> GalR1 = GalR2. In forebrain regions the ranking was GalR1 > galanin > GalR2. VGLUT1 and -2 were strongly expressed in the pontine nuclei but could not be detected in LC or serotonin neurons. VGLUT2 transcripts were found in very small, nonpigmented cells in the LC and in the lateral and dorsal aspects of the periaqueductal central gray. Nitric oxide synthase was not detected in serotonin neurons. These findings show distinct differences between the human brain and rodents, especially rat, in the distribution of the galanin system and some other transmitter systems. For example, GalR3 seems to be the important galanin receptor in both the human LC and DRN versus GalR1 and -2 in the rodent brain. Such knowledge may be important when considering therapeutic principles and drug development.he locus coeruleus (LC) and the dorsal raphe nucleus (DRN)/raphe median nucleus (MRN) have been the focus of clinical and preclinical monoamine research for almost half a century. Using the formaldehyde fluorescence (Falck-Hillarp) method (1), Dahlström and Fuxe (2) originally described these nuclei in the rat as containing noradrenaline (NA) (the A6 group) and 5-hydroxytryptamine (5-HT; serotonin) (the B7/8 groups), respectively. The LC harbors 2,800-3,600 neurons with an additional 260 neurons in the subcoeruleus area, the great majority of which are noradrenergic (3-6).The DRN forms a rostro-caudal, ventral midline column and is part of the periaqueductal central gray (PAG) (7) with a large number of 5-HT neurons that can be subdivided into several subgroups (2,(8)(9)(10)(11). Both the NA-LC (5, 6, 12) and the 5HT-DRN (8-11, 13) neurons have wide projections to most forebrain areas.In humans the LC is a compact, blue-pigmented nucleus consisting of a total of ∼50,000 neurons (both sides), almost all of which are noradrenergic (14-16). The DRN comprises about 165,000 5-HT neurons, which constitute around 70% of all DRN neurons (17). Thus, there are numerous nonserotonergic neurons in the human DRN, as is also the case in other species, including the mouse (18,19).It now is well established that most neurons synthesize and release several types of messenger molecules in the process known as "cotransmission" (20-26). For example, in the rat some serotonergic DRN neurons synthesize nitric oxide (NO), visualized as N...

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Association of galanin haplotypes with alcoholism and anxiety in two ethnically distinct populations

Cited by 73 publications

References 44 publications

Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating Triglycerides

Effect of Ethanol on Hypothalamic Opioid Peptides, Enkephalin, and Dynorphin: Relationship With Circulating Triglycerides

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

Distinct features of neurotransmitter systems in the human brain with focus on the galanin system in locus coeruleus and dorsal raphe

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