Inhibition of fear potentiated startle in rats following peripheral administration of secretin

Myers, Karyn M.; Goulet, M; Rusche, James R.; Boismenu, Richard; Davis, Michael

doi:10.1007/s00213-003-1633-5

Cited by 20 publications

(10 citation statements)

References 36 publications

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“…To our knowledge only one other neuropeptide or neuropeptide-mimetic, has been shown to block FPS. In this regard, Myers et al (2004) reported that secretin, a neurohormone neuropeptide, reduced FPS after systemic administration.…”

Section: Discussionmentioning

confidence: 99%

The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle

Shilling

Feifel

2008

Pharmacology Biochemistry and Behavior

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Preliminary evidence suggests that the neuropeptide, neurotensin (NT) may regulate fear/anxiety circuits. We investigated the effects of PD149163, a NT-1 receptor agonist, on fear-potentiated startle (FPS). Sprague Dawley rats were trained to associate a white light with a mild foot shock. In one experiment, animals were treated with either subcutaneous vehicle or PD149163 (0.01, 0.1 or 1.0 mg/kg) twenty-four hours after training. Twenty minutes later their acoustic startle response in the presence or absence of the white light was tested. In a second experiment, saline and 1.0 mg/kg PD149163 were tested using a separate group of rats. In the first experiment, PD149163 produced a non-significant decrease in baseline acoustic startle at all three doses. As expected, saline treated rats exhibited significant FPS. An ANOVA of percentage FPS revealed no significant effect of treatment group overall but the high dose group did not display FPS strongly suggesting an FPS effect at this dose. This finding was confirmed in the second experiment where the high dose of PD149163 reduced percent FPS relative to saline (P<0.05). These data suggest that systemically administered NT-1 agonists modulate the neural circuitry that regulates fear and anxiety to produce dose-dependent anxiolytic-like effects on FPS.

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Section: Discussionmentioning

confidence: 99%

The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle

Shilling

Feifel

2008

Pharmacology Biochemistry and Behavior

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“…This paradigm is therefore used as an important laboratory model of anxiety, both in animals [301, 369, 408, 498] and humans [11, 144, 147, 210]. The LC may contribute to the activation of the startle pathway in the fear-potentiated startle paradigm in two ways.…”

Section: Physiological Manipulation Of Locus Coeruleus Activitymentioning

confidence: 99%

“…This observation opens the way to consider retrograde vagus nerve stimulation as a possible indication for AD, and indeed preliminary reports indicate that this procedure may have beneficial effects on cognitive functions in patients suffering from AD [285, 414]. The electrical stimulation of the left vagus nerve is well established as a therapeutic procedure both in epilepsy [149] and treatment-resistant depression [301]. Interestingly, it has been shown that vagus nerve stimulation leads to increases in the firing rates of noradrenergic neurones in the LC and serotonergic neurones in the dorsal raphe nucleus [103].…”

Section: Pathological Alterations Of Locus Coeruleus Activitymentioning

confidence: 99%

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

Samuels

Szabadi²

2008

403

365

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The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson’s and Alzheimer’s diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, α2-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including α2-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system.

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“…Intravenous (IV) administration of secretin at a clinical dose was shown to pass through Blood-BrainBarrier [4] and that the peptide was transported into the brain by non-saturable transmembrane diffusion [2,4]. Besides, it was also shown that peripheral, IV, or intraperitoneal (IP) administered secretin could lead to i) c-fos expression changes in discrete brain regions, including NTS [128] and the central nucleus of amygdala [136]; ii) re-establishment of the communicative and affiliative interactions in autistic children [118]; and iii) modulation of neural networks in the acquisition and expression of emotional behaviors, including fear and anxiety [137]. Collectively, it is possible that endogenously synthesized secretin, either in the CNS or from peripheral endocrine tissues, acts in the neuronal network within prosencephalon, mesencephalon, and rhombencephalon to exert its central actions.…”

Section: Secretinmentioning

confidence: 99%

The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

Chu¹,

Lee²,

Siu³

et al. 2006

CNSAMC

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The secretin/PACAP/VIP superfamily contains at least ten brain-gut peptides, including secretin, pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), glucagon, glucagon-like peptide-1 (GLP-1), glucagon like peptide-2 (GLP-2), gastric inhibitory polypeptide (GIP), peptide histidine isoleucine (PHI) or peptide histidine methionine (PHM), and growth hormone-releasing hormone (GHRH). These peptides exhibit a wide tissue distribution in the peripheral systems, indicating their pleiotrophic actions in the body. Meanwhile, their functions in the central nervious system (CNS) have also been consolidated recently. For instance, most of these peptides have shown to serve as neurotransmitters, neuromodulators, neurotrophic factors, and/or neurohormones in the brain, and hence, their potential as novel CNS agents in treating neurological disorders including Autism, Alzheimer's disease, Parkinson's disease and HIV-associated neuronal cell death were recently exploited. In this article, recent progress in research of peptides in this family with particular emphasis on structures, their central functions and potential use in the treatment of neuronal diseases are reviewed.

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Inhibition of fear potentiated startle in rats following peripheral administration of secretin

Abstract: This investigation provides additional evidence that systemically administered secretin can influence a neural network implicated in the acquisition and expression of emotional behaviors, including fear and anxiety.

Cited by 20 publications

References 36 publications

The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle

The neurotensin-1 receptor agonist PD149163 blocks fear-potentiated startle

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part II: Physiological and Pharmacological Manipulations and Pathological Alterations of Locus Coeruleus Activity in Humans

The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

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