Upregulation of Galanin Binding Sites and GalR1 mRNA Levels in the Mouse Locus Coeruleus Following Chronic Morphine Treatments and Precipitated Morphine Withdrawal

Zachariou, Venetia; Thome, Johannes; Parikh, Kavita; Picciotto, Marina R.

doi:10.1016/s0893-133x(00)00094-4

Cited by 34 publications

(50 citation statements)

References 28 publications

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“…Furthermore, mRNA expression does not correlate with posttranscriptional protein regulation or protein localization to nerve terminals. Ultimately, the most prominent areas of GalR1, GalR2, and GalR3 immunoreactivity correlate with the detection of mRNA transcripts in all published reports of galanin receptor mRNA distribution (Burgevin et al, 1995;Wang et al, 1997b;Kolakowski et al, 1998;Smith et al, 1998;O'Donnell et al, 1999;Zachariou et al, 2000;Crawley et al, 2002;Mennicken et al, 2002;Hohmann et al, 2003;Shen et al, 2003).…”

Section: Discussionmentioning

confidence: 59%

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Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain

Hawes

Picciotto

2004

J of Comparative Neurology

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The distribution of immunoreactivity for the three identified neuropeptide galanin receptors, GalR1, GalR2, and GalR3, was determined in areas of the mouse brain involved in drug addiction, including the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NA), and locus coeruleus (LC). All three galanin receptors are found in the VTA, SN, NA, and LC; however, GalR1 protein is most highly represented in the VTA, NA, and SN, suggesting that GalR1 may play a predominant role in galanin-mediated regulation of dopamine neurotransmission. GalR1 and GalR3 protein levels are high in the LC, suggesting that these isoforms may be important for galanin-mediated regulation of noradrenergic transmission during opiate withdrawal. Although the distribution of GalR1, GalR2, and GalR3 largely recapitulates the pattern of galanin binding throughout the brain, some discrepancies exist, suggesting that another galanin receptor(s) may be present in some brain areas. Overall, GalR1, GalR2, and GalR3 are distributed widely throughout the brain, correlate with widespread galanin binding, and colocalize with tyrosine hydroxylase in catecholaminergic brain areas.

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Section: Discussionmentioning

confidence: 59%

“…Galanin equilibrium binding experiments were performed as previously described (Zachariou et al, 2000). Fourteen micrometer coronal brain sections were cut on a cryostat and collected on gelatinized slides at the same bregma positions as those used for the immunohistochemistry experiments.…”

Section: Galanin Bindingmentioning

confidence: 99%

Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain

Hawes

Picciotto

2004

J of Comparative Neurology

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“…Galanin receptors are modulated during opiate dependence, because both galanin receptor levels, as measured by radioligand binding, and GalR1 mRNA levels are increased in the LC after opiate withdrawal (9). In contrast, galanin peptide mRNA levels do not change during withdrawal (31).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, galanin inhibits the firing of locus coeruleus (LC) neurons (6), which may affect expression of opiate withdrawal signs (7). Further, stress increases galanin mRNA in the LC (8), and at least one galanin receptor subtype, GalR1, is up-regulated in the LC during opiate withdrawal (9). Thus, galanin may counteract opiate withdrawal through effects on the noradrenergic system.…”

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confidence: 99%

The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal

Zachariou

Brunzell

Hawes

et al. 2003

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

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Much research has focused on pathways leading to opiate addiction. Pathways opposing addiction are more difficult to study but may be critical in developing interventions to combat drug dependence and withdrawal. Galanin decreases firing of locus coeruleus neurons, an effect hypothesized to decrease signs of opiate withdrawal. The current study addresses whether galanin affects morphine withdrawal signs by using a galanin agonist, galnon, that crosses the blood-brain barrier, and mice genetically engineered to under-or overexpress galanin peptide. Galnon significantly decreased morphine withdrawal signs in C57BL͞6 mice. Further, knockout mice lacking galanin showed exacerbated morphine withdrawal signs, suggesting that endogenous galanin normally counteracts opiate withdrawal. Transgenic mice overexpressing galanin in noradrenergic neurons also showed decreased morphine withdrawal signs, suggesting a possible neuroanatomical locus for these effects of galanin. Both c-fos immunoreactivity, a marker of neuronal activity, and phosphorylation of tyrosine hydroxylase at Ser-40, a marker of cAMP levels, are decreased in the locus coeruleus by galnon treatment after morphine withdrawal, suggesting a possible molecular mechanism for the behavioral effects of galanin. These studies suggest that galanin normally acts to counteract opiate withdrawal and that small molecule galanin agonists could be effective in diminishing the physical signs of withdrawal.

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“…As noted above, galanin receptor mRNAs [46] and galanin binding sites [28] are expressed in neurons in the mesolimbic DA system. In striatum, GalR1 mRNA is expressed in a pattern that suggests that it is localized in cholinergic interneurons [47,48], but specific galanin binding sites are much more widespread [28], suggesting that galanin receptors may be represented on neuronal terminals in the striatum and NAc. Consistent with the ability of galanin to decrease morphine place preference, galanin has an inhibitory effect on DA release in rat striatal slices [49].…”

Section: Regulation Of the Dopaminergic And Cholinergic Systems By Gamentioning

confidence: 99%

Galanin – 25 years with a multitalented neuropeptide

Picciotto

2008

Cell. Mol. Life Sci.

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There has been increasing interest in the ability of neuropeptides involved in feeding to modulate circuits important for responses to drugs of abuse. A number of peptides with effects on hypothalamic function also modulate the mesolimbic dopamine system (ventral tegmental area and nucleus accumbens). Similarly, common stress-related pathways can modulate food intake, drug reward and symptoms of drug withdrawal. Galanin promotes food intake and the analgesic properties of opiates; thus it initially seemed possible that galanin might potentiate opiate reinforcement. Instead, galanin agonists decrease opiate reward, measured by conditioned place preference, and opiate withdrawal signs, whereas opiate reward and withdrawal are increased in knock-out mice lacking galanin. This is consistent with studies showing that galanin decreases activity-evoked dopamine release in striatal slices and decreases the firing rate of noradrenergic neurons in locus coeruleus, areas involved in drug reward and withdrawal, respectively. These data suggest that polymorphisms in genes encoding galanin or galanin receptors might be associated with susceptibility to opiate abuse. Further, galanin receptors might be potential targets for development of novel treatments for addiction.

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Upregulation of Galanin Binding Sites and GalR1 mRNA Levels in the Mouse Locus Coeruleus Following Chronic Morphine Treatments and Precipitated Morphine Withdrawal

Abstract: The neuropeptide galanin and its receptors are expressed in the locus coeruleus (LC), a brain area

Cited by 34 publications

References 28 publications

Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain

Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain

The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal

Galanin – 25 years with a multitalented neuropeptide

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