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Galanin (GAL) is a 29 amino acid peptide, first identified from the porcine intestine and widely distributed within the brain and peripheral tissues. Among GAL biological functions, its role as a potent appetite-stimulating peptide is probably the most studied. With galanin's established role in the modulation of food intake in fish, this study aims to evaluate the effects of GAL on the intestinal motility of the goldfish, Carassius auratus, using an organ bath system. Our results found that application of GAL to the organ bath causes a significant concentration-dependent decrease in the amplitude of spontaneous contractions of goldfish gut. Preincubations of intestinal strips with acetylcholine (ACh) and GAL showed that GAL increases the force of ACh-induced contractions of the goldfish gut. These results provide the first evidence for a role of GAL in gut motility in goldfish. This also suggests a crosstalk between the effects of GAL and ACh in such functions, thus pointing to a putative joint role between the two molecules. These findings offer novel information that strengthens the role of the galaninergic system in fish feeding., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Thromboembolic complications are a significant cause of mortality and re-hospitalization in heart failure (HF) patients. One source of thrombi is the ventricular endocardial surface that becomes increasingly pro-thrombotic as HF progresses. Anticoagulation comes with bleeding risks so identifying therapeutic agents for improving cardiac endothelial health are of critical clinical importance. Endocardial endothelial cells are closely apposed to cardiac sympathetic nerves. In HF, cardiac sympathetic nerves are dysregulated and promote disease progression. Whether endocardial endothelial health and function is impacted by sympathetic dysregulation in HF is unknown. Also unexplored is the impact of neuropeptides, such as galanin and neuropeptide Y (NPY), co-released from sympathetic nerve terminals, on endothelial health. In this study we examined the effect of sympathetic nerve-released neurotransmitters and neuropeptides on the procoagulant phenotype of cultured human endocardial endothelial cells from HF patients. As a functional readout of procoagulant state we examined thrombin-mediated von Willebrand factor (vWF) extrusion and multimer expression. We demonstrate that vWF extrusion and multimer expression is promoted by thrombin, that isoproterenol (a beta-adrenergic receptor agonist) augments this effect, whereas co-treatment with the beta-blockers propranolol and carvedilol blocks this effect. We also show that vWF extrusion and multimer expression is attenuated by treatment with the neuropeptide galanin, but not with NPY. Our results are consistent with a protective role of beta-blockers and galanin on endocardial endothelial health in heart failure. Improving endothelial health through galanin therapy is a future clinical application of this study., (Copyright © 2017. Published by Elsevier B.V.)

Several studies have shown that injury to the central and peripheral nervous system can increase expression of galanin, a 29 amino acid neuropeptide. Moreover, there is evidence that galanin, especially through its galanin receptor 2 (GalR2) receptor, plays a neuroprotective role in different injury models. However, direct studies of a possible neuroprotective effect of galanin in experimental stroke models are lacking. Galanin, a GalR2/3 agonist or artificial CSF was continuously infused intracerebroventricularly (i.c.v.) in naïve female rats after a 60min transient and focal occlusion of the middle cerebral artery. The animals were sacrificed, and the ischemic lesion was visualized using 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining. The lesion was 98% larger after i.c.v. administration of the GalR2/3 agonist (2.4nmol/day) seven days after occlusion compared to artificial CSF (p=0.023). No statistically significant differences were found after seven days in the groups treated with galanin in three different concentrations (0.24, 2.4 and 24nmol/day; p=0.939, 0.715 and 0.977, respectively). There was no difference in the size of the ischemic lesions measured after three days in the galanin-treated group (2.4nmol/d) compared to artificial CSF (p=0.925). The present results show, surprisingly, that a GalR2/3 agonist doubled the size of the ischemic lesion. Whether this effect primarily reflects the properties of the current model, species, gender and/or the mode of galanin administration, e.g. causing desensitization, or whether galanin indeed lacks neuroprotective effect of its own, remains to be corroborated., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The effect of intracerebroventricular infusion of galanin and/or the galanin antagonist M35 was studied in the forced swim test. Animals were pre-exposed to water for 15 min 24 h prior to test. Immobility and climbing were assessed during the second, 5 min exposure to water. Rats receiving a single infusion of galanin (3 nmol) displayed a significant increase of immobility. This effect was blocked by co-administration of M35 (1 nmol). M35 alone (1 nmol) produced a significant decrease of immobility. The results further support the hypothesis that galanin may play a role in mood disorders, and that galanin antagonists may represent new candidates for antidepressant treatment.

The neuropeptide galanin impairs learning and memory in rodents. The mechanism underlying the cognitive effects of galanin may be related to inhibitory effects of galanin on cholinergic transmission. As cholinergic function is thought to modulate sustained attention, the present study examined whether galanin-overexpressing transgenic mice have impairments in sustained attention. Galanin transgenic (GAL-tg) mice and wild-type (WT) littermate controls were trained in a 5-choice serial reaction time task, modified to assess sustained attention. GAL-tg and WT mice performed similarly during acquisition with respect to accuracy, total omissions, and response speed. Attentional mechanisms were challenged by parametric changes including increased event rate, event asynchrony, or decreased stimulus duration. Singly, these challenges did not differentially affect performance between genotypes. Concurrent administration of these challenges, which represents an optimal test of sustained attention, also had similar effects on GAL-tg and WT mice. When stimulus discriminability was reduced by constant illumination of the house light, GAL-tg mice omitted more trials than WT mice, but other measures of performance did not differ by genotype. Moreover, intraventricular injection of galanin in WT mice did not affect sustained attention. These data indicate that previously reported learning and memory effects of galanin are not secondary to attentional dysfunction.

Galanin (GAL) has been implicated in modulating anxiety, although a precise role remains unclear. Previous studies revealed anxiolytic effects, anxiogenic effects, or no effect, depending on the test, brain region, route of drug administration and context. We have shown previously that microinjection of the GAL antagonist M40 into central amygdala blocked an anxiolytic response to acute stress on the elevated plus maze when rats were pretreated with yohimbine, suggesting an anxiolytic effect of GAL. By contrast, we also showed that microinjection of M40 into the lateral bed nucleus of the stria terminalis attenuated anxiety-like behavioral responses to stress on the plus maze and social interaction tests, implying an anxiogenic effect for GAL. The behavioral response to stress on both these tests is a reduction of an ongoing behavior (open-arm exploration or social interaction, respectively). To better understand the anxiety-modulating role of GAL, it is also important to ascertain its effect on a response that represents an activation rather than suppression of behavior. Thus, in this study, we investigated an active behavioral response to acute stress in rats, the shock-probe defensive burying response. Bilateral microinjections of M40 into lateral septum (LS), a region important to this response and innervated by GAL, dose-dependently decreased burying without affecting immobility. No change was seen in hindpaw withdrawal latency on a thermosensitivity assay, suggesting that the reduction in burying behavior was not attributable to changes in cutaneous pain sensitivity. These results indicate that in LS, GAL facilitates the active anxiety-like behavioral response on the defensive burying test, similar to its facilitatory effect on anxiety-like stress-induced suppression of behavior in the lateral bed nucleus. These results highlight the fact that, rather than a unified system-like role in modulating anxiety, the effects of GAL can be either facilitating or attenuating, and are region-specific, context-specific and response-specific.

The 29/30 amino acid neuropeptide galanin coexists with vasopressin in the hypothalamus and has been shown to inhibit the actions of vasopressin and aldosterone, suggesting an inhibitory role for galanin in physiological water retention mechanisms and water seeking and water consumption behavior. Little work, however, has examined a role for galanin in water intake regulation. Furthermore, many experiments that have reported galanin-induced impairments in the performance of tasks thought to measure learning and memory have used water restriction routines and water reinforcers to maintain responding. Therefore, the present study examined the effects of intracerebroventricularly administered galanin (5.0-20.0 microg/5 microl) on free water consumption during a 10 min test session and a follow up open field exploration, an operant progressive ratio (PR) schedule, a test used to assess reinforcer strength, and an operant fixed time schedule (FT 20) in 23.5h water restricted rats. Finally, in an additional experiment that was designed to simulate the effects of a galanin-induced decrease in water reinforcer efficacy, the rats were allowed access to water prior to testing in an operant delayed non-matching to position (DNMTP) task. A galanin-induced decrease in water consumption was observed in both the free access test and the FT 20 at the 20 microg dose, but no significant galanin-induced alterations in open field behavior. A decrease in responses emitted and rewards received was observed on the PR schedule at the 5, 10, and 20 microg doses. Pre-session access to water significantly reduced the number of trials per session in the DNMTP but did not reduce accuracy. This study is the first to observe a galanin-induced reduction in water intake and reinforced operant behavior, and suggests that galanin may play a role in regulating water intake and reinforcement. However, the present data also suggest that DNMTP choice accuracy deficits observed previously cannot be attributed to a galanin-induced change in reinforcer efficacy.

Neuropeptide Y (NPY) and galanin (GAL) are densely localized in brain regions subserving stress, fear and anxiety. While previous research supports a role for both neuropeptides in the mediation of rodent emotional behaviors, there is currently a lack of information on the effects of central administration of NPY and GAL on fear- and anxiety-related behaviors in mice. In the present study, the effects of intracerebroventricularly administered NPY and GAL were assessed in C57BL/6J mice on a battery of tests for fear- and anxiety-related behavior. NPY (0.5, 1.0 nmol) produced clear anxiolytic-like effects in the elevated plus-maze and light<-->dark exploration test, whereas GAL (0.5, 1.0 nmol) was without effect. NPY (0.5 nmol) also increased locomotor activity in the open field test. In the fear conditioning paradigm, NPY administered prior to training reduced freezing to context (0.5, 1.0 nmol) and auditory cue (1.0 nmol). Pre-training GAL (0.5 nmol) treatment reduced freezing to context. Taken together, results demonstrate robust effects of centrally-administered NPY, but not GAL, on anxiety-like behaviors and fear conditioning in mice. These findings provide a basis for future studies of mice with targeted gene mutations, directed at delineating the anatomical regions and receptor subtypes mediating the effects of NPY and GAL on emotion.

Galanin is a neuropeptide that has been implicated in multiple bioactivities, inter alia eating disorders. In this study, we have examined the effects of galnon, a novel low molecular weight galanin receptor ligand. Previous studies have shown that galnon acts as a systemically active, blood-brain barrier crossing agonist on galanin signaling both in vitro and in vivo, inhibiting pentylenetetrazole-induced seizures. Here, intracerebroventricular (10-20 microg) and intraperitoneal (1.5-5 mg/kg) administration of galnon induced a strong, dose-dependent reduction of food intake in rats and mice. This reduction in feeding occurred without reducing general activity and was shown to be attenuated by an intracerebroventricular administration of M35, a peptide galanin antagonist. These data demonstrate that galnon is a promising tool for studies of the involvement of galanin in feeding disorders and other behavioral processes.

In order to study the role of endogenous somatostatin in the physiologic modulation of REM sleep (REMS), we measured the effect of intracerebroventricular (ICV) injection of somatostatin antagonist (SA) cyclo-(7-aminoheptanoyl-phe-d-trp-lys-thr(bzl)) on sleep in rats. The effect of ICV SA was also tested after 24-h REMS deprivation with the platform method. To study the role of locus coeruleus (LC) as a site of the sleep inducing action for somatostatin and galanin we microinjected SA, somatostatin, and galanin locally into LC. In all experiments, vigilance state was analyzed visually from 6 h post-injection EEG/EMG recording. Injection of 0.5 and 2 nmol of SA ICV reduced spontaneous REMS and 2 nmol dose reduced also rebound REMS after REMS deprivation when compared with controls (artificial cerebrospinal fluid vehicle). Microinjection of 0.25 nmol of SA into LC reduced REMS, whereas microinjection of somatostatin, galanin, and a combined injection of them were not effective to induce REMS. The results suggest that endogenous somatostatin may contribute to facilitation of REMS. Somatostatin receptors in the LC may be one possible mediator of this effect.

The present study was performed on rats with experimental mononeuropathy induced by left common sciatic nerve loose ligation. Unilateral sciatic nerve loose ligation induced decreases of the hindpaw withdrawal latency to the hot-plate test, cold-plate test and the Randall Selitto test. Sciatic nerve loose ligation induced hyperesponsiveness to touch at room temperature also. Intrathecal administration of either 3 or 6 nmol of galanin, but not 1 nmol, induced significant bilateral increases in hindpaw withdrawal latencies to the hot-plate test, cold-plate test and the Randall Selitto tests in rats with left mononeuropathy. The results indicate that galanin may play important roles in transmission of presumed nociceptive information in the spinal cord of mononeuropathic rats.