The role of the neuropeptide galanin in forming type-specific behavioral characteristics.
ABSTRACT Intranasal administration of a galanin receptor blocker to rats was found to change their behavioral type on being placed in an unfamiliar environment, with decreases in movement and investigative activity and increases in the level of anxiety in the open field test. The basal level of expression of the galanin precursor mRNA in the anterior hypothalamus was significantly higher in rats with the active type of behavior in the open field test. In conditions of galanin receptor blockade, there was also a faster increase in the serum corticosterone level in response to a stress situation (forced swimming test), which was accompanied by a reduction in the immobilization time. These data support the involvement of galanin in the formation of individual-typological behavioral characteristics and demonstrate its important role in adaptation to stress.
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ABSTRACT: Converging evidence implicates the regulatory neuropeptide galanin in anxiety- and depression-related behaviors, through modulation of neuroendocrine, serotonergic, and noradrenergic systems. This study examined the relationship between stress-induced posttraumatic stress disorder (PTSD)-like behavioral response patterns in rats and galanin mRNA levels in key brain areas and the effects of acute phase pharmacologic manipulation using an agonist (galnon) on behavioral, physiologic, and response patterns of brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine-1A (5HT-1A). Galanin mRNA expression was assessed in the frontal cortex and hippocampus in the short- and long-term (30 min and 7 days) after exposure to predator scent stress. The effects of intraperitoneal galnon .5 mg/kg versus saline 1 hour postexposure on behavioral tests (elevated plus maze and acoustic startle response) were evaluated 7 days later. Trauma-cue response, circulating corticosterone, and localized brain expression of 5HT-1A receptors and BDNF were subsequently assessed. All data were analyzed in relation to individual behavior patterns. Whereas animals with minimal behavioral disruption displayed a lasting upregulation of galanin mRNA in the hippocampal CA1 area, those with extreme behavioral responses displayed downregulation in both CA1 and frontal cortex. Immediate postexposure treatment with galnon significantly reduced prevalence rates of extreme responders, reduced trauma-cue freezing responses, corrected the corticosterone response, and increased CA1 expression of 5HT-1A and BDNF mRNA compared with saline controls. Galanin is actively involved in the neurobiological response to predator scent stress with resilience/recovery after stress exposure and thus warrants further study as a potential therapeutic avenue for the treatment of anxiety-related disorders.Biological psychiatry 03/2009; 65(5):383-91. DOI:10.1016/j.biopsych.2008.10.034 · 9.47 Impact Factor
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ABSTRACT: In recent years, studies have advocated neuropeptide systems as modulators for the behavioral states found in mood disorders such as depression and anxiety disorders. Neuropeptides have been tested in traditional animal models and screening procedures that have been validated by known antidepressants and anxiolytics. However, it has become clear that although these tests are very useful, neuropeptides have distinct behavioral effects and dose-dependent characteristics, and therefore, use of these tests with neuropeptides must be done with an understanding of their unique characteristics. This review will focus on the behavioral actions of neuropeptides and their synthetic analogs, particularly in studies utilizing various preclinical tests of depression and anxiety. Specifically, the following neuropeptide systems will be reviewed: corticotropin-releasing factor (CRF), urocortin (Ucn), teneurin C-terminal associated peptide (TCAP), neuropeptide Y (NPY), arginine vasopressin (AVP), oxytocin, the Tyr-MIF-1 family, cholecystokinin (CCK), galanin, and substance P. These neuropeptide systems each have a unique role in the regulation of stress-like behavior, and therefore provide intriguing therapeutic targets for mood disorder treatment.Peptides 12/2009; 31(4):736-56. DOI:10.1016/j.peptides.2009.12.015 · 2.61 Impact Factor
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ABSTRACT: BACKGROUND: Alcoholism is a heterogeneous disease, with subjects possibly differing both in the best measure that predicts their excess consumption and in their most effective pharmacotherapy. Two different measures, high novelty-induced activity and high-fat-induced triglycerides (TGs), are known to identify subgroups of animals prone to consuming higher amounts of ethanol (EtOH). The question investigated here is whether these subgroups are, in fact, similar in their neurochemical phenotype that may contribute to their overconsumption. METHODS: EtOH-naïve, Sprague-Dawley rats were subgrouped based on the 2 predictor measures of activity or TG levels, and then quantitative real-time polymerase chain reaction and digoxigenin-labeled in situ hybridization were used to measure their expression of hypothalamic peptides that affect EtOH intake. In additional subgroups subsequently trained to drink 9% EtOH, the opioid antagonist and alcoholism medication, naltrexone, was tested at a low dose (0.02 mg/kg, s.c.) to determine the rats' sensitivity to its effects. RESULTS: The 2 measures, while both effective in predicting amount of EtOH intake, were found to identify distinctive subgroups. Rats with high compared to low activity exhibited significantly greater expression of galanin and enkephalin in the paraventricular nucleus (PVN) and of orexin in the perifornical lateral hypothalamus (PFLH), but no difference in melanin-concentrating hormone in PFLH or neuropeptide Y in arcuate nucleus. This contrasts with rats having high TG, which exhibited greater expression only of PVN galanin, along with reduced PFLH orexin. The high-activity rats with elevated enkephalin, but not high-TG rats, were also unusually sensitive to naltrexone, which significantly reduced their alcohol intake. CONCLUSIONS: In addition to revealing differences in endogenous peptides and drug responsiveness in predicted high EtOH drinkers, this study demonstrates that these disturbances differ markedly between the 2 at-risk subgroups. This indicates that simple tests may be effective in identifying subjects most responsive to a specific pharmacotherapy.Alcoholism Clinical and Experimental Research 06/2012; 37. DOI:10.1111/j.1530-0277.2012.01858.x · 3.31 Impact Factor