ICV-CRH potently affects behavior without altering antinociceptive responding

doi:10.1016/0024-3205(86)90523-0

Life Sciences

Volume 39, Issue 5, 4 August 1986, Pages 433-441

https://doi.org/10.1016/0024-3205(86)90523-0 Get rights and content

Abstract

To explore the hypothesized integrative function of corticotropin releasing hormone (CRH) in the stress response, stress-related behaviors including antinociception were studied in rats after either intracerebroventricular (ICV) or peripheral administration of CRH. The effects of low-dose (0.3 ωg) and high-dose (3.0 ωg) ICVCRH were compared to those of vehicle, employing a within- $S$ design. The two doses yielded comparable behavioral changes suggestive of increased arousal and stress. These changes were characterized by significant increases in grooming, walking, burrowing, self-gnawing, and pica, and decreases in rearing and sleeping. None of these effects of ICVCRH were obtained with peripheral administration of the same doses. The hot-plate test of analgesia failed to show a significant effect of ICVCRH or peripherally administered CRH. A between- $S$ experiment incorporating both the tail-flick and the hot-plate tests of analgesia compared ICVCRH (3.0 ωg) with vehicle. ICVCRH did not affect antinociceptive responding in either of these tests. In contrast, ICV morphine (10 ωg) yielded potent analgesia in both tests. Thus, with doses of ICVCRH yielding clear evidence of stress-related behavior, no evidence of analgesia was obtained. These findings question the possible role of central CRH systems in antinociceptive processes.

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Anxiolytic effect of the GPR103 receptor agonist peptide P550 (homolog of neuropeptide 26RFa) in mice. Involvement of neurotransmitters
2016, Peptides
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Takayasu et al. demonstrated that 43RFa – an endogenous ligand of the GPR103 receptor – increased significantly the general locomotor activity and the number of grooming bouts as well as the time spent in grooming in mice [34]. The exploratory behavior (locomotion) and the stereotyped behavior (grooming) are under the control of Corticotropin-releasing hormone (CRH) release, especially through the activation of the mesolimbic CRH1 receptor system [1,21,31,33]. Therefore, one can presume that 43RFa may increase the CRH release and stimulate the hypothalamic–pituitary–adrenal (HPA) axis.
The GPR103 receptor is a G protein-coupled receptor, which plays a role in several physiological functions. However, the role of the GPR103 receptor in anxiety has not been clarified. The first aim of our study was to elucidate the involvement of the GPR103 receptor in anxious behavior. Mice were treated with peptide P550, which is the mouse homolog of neuropeptide 26RFa and has similar activity for the GPR103 receptor as neuropeptide 26RFa. The anxious behavior was investigated using an elevated plus-maze paradigm. The second aim of our study was to investigate the underlying neurotransmissions. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABA_A) receptor antagonist, bicuculline, a non-selective 5-HT₂ serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT₁/5-HT₂ serotonergic receptor antagonist, methysergide, a D₂, D₃, D₄ dopamine receptor antagonist, haloperidol, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a nonselective β-adrenergic receptor antagonist, propranolol. Our results demonstrated that peptide P550 reduces anxious behavior in elevated plus maze test in mice. Our study shows also that GABA_A-ergic, α- and β-adrenergic transmissions are all involved in this action, whereas 5-HT₁ and 5-HT₂ serotonergic, muscarinic cholinergic and D₂, D₃, D₄ dopaminergic mechanisms may not be implicated.
The actions of neuropeptide SF on the hypothalamic-pituitary-adrenal axis and behavior in rats
2013, Regulatory Peptides
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In conclusion, our data suggest that centrally released NPSF, acting at the paraventricular nucleus [38] stimulates CRH secretion. This, in turn, leads to ACTH secretion and also modulates, although in different manner than other PQRFamides, the accompanying behavioral phenomena related to the stress response [39,40]. Further studies are necessary, however, to clarify the signal transduction processes of individual PQRFamides, separate their distinct activities and outline the physiological profile of NPFF and NPVF on the HPA axis and behavior.
Present experiments focused on measuring the effect of neuropeptide SF (NPSF) on the hypothalamus–pituitary–adrenal (HPA) axis and behavior. The peptide was administered in different doses (0.25, 0.5, 1, 2 μg) intracerebroventricularly to rats, and the behavior of which was then observed by telemetry and open-field test. Effect of NPSF on core temperature was also measured via telemetry. Plasma ACTH and corticosterone concentrations were measured to assess the influence of NPSF on the HPA activation. In addition, the changes in corticotrophin-releasing hormone (CRH) level in the hypothalamic paraventricular nucleus were continuously monitored by means of intracerebral microdialysis. Our results showed that NPSF augmented paraventricular CRH release and increased ACTH and corticosterone levels in the plasma. The release of corticosterone was successfully blocked by the pre-treatment of the CRH antagonist α-helical CRH_9–41. Spontaneous and exploratory locomotor activity was also stimulated according to the telemetric and open-field studies. However, NPSF only tended to alter stereotyped behavior in the open-field experiments. These results demonstrate that NPSF may play a physiologic role in the regulation of such circadian functions as the activity of motor centers and the HPA axis, through the release of CRH.
CRH: The link between hormonal-, metabolic- and behavioral responses to stress
2013, Journal of Chemical Neuroanatomy
Citation Excerpt :
Furthermore, CRH overexpressing mice also display a behavioral phenotype seen in stressed animals including increased anxiety (Kasahara et al., 2007; Stenzel-Poore et al., 1996). CRH increases locomotion in a familiar surroundings, decreases exploration in novel environment, induces grooming, burrowing, self-gnawing and decreases rearing and sleeping (Sherman and Kalin, 1986), however does not affect analgesia. Some of these behaviors (grooming and exploration) can be initiated by CRH microinjections into the amygdala under resting conditions (Wiersma et al., 1995).
Two major and mutually interconnected brain systems are recruited during stress reaction. One is the hypothalamic paraventricular nucleus (PVH) and the second is the extended amygdala. PVH governs the neuroendocrine stress response while CeA regulates most of the autonomic and behavioral stress reactions. The common neurohormonal mediator of these responses is the corticotropin-releasing hormone, CRH, which is expressed in both centers. CRH belongs to a larger family of neuropeptides that also includes urocortins 1, 2, and 3 all have different affinity toward the two types of CRHR receptors and have been implicated in regulation of stress and HPA axis activity. One functionally relevant aspect of CRH systems is their differential regulation by glucocorticoids. While corticosterone inhibits CRH transcription in the PVH, stress-induced glucocorticoids stimulate CRH expression in the extended amygdala. This review summarizes past and recent findings related to CRH gene regulation and its involvement in the neuroendocrine, autonomic and behavioral stress reaction.
Atrazine does not induce pica behavior at doses that increase hypothalamic-pituitary-adrenal axis activation and cause conditioned taste avoidance
2012, Neurotoxicology and Teratology
Citation Excerpt :
For example, activation of the HPA-axis through intracerebroventricular (ICV) injection of corticotrophin releasing factor (CRF) causes a percentage increase in CORT release that is similar during both the light and dark phases (Atkinson et al., 2006; Dubovicky et al., 2007). In addition, activation of the HPA-axis with ICV administration of CRF during the dark phase is effective in inducing pica behavior and decreases in food intake, despite the presence of already elevated diurnal CORT concentrations (Sherman and Kalin, 1986; Morley and Levine, 1982). This suggests that although diurnal serum levels of CORT were high at the time of behavioral testing, alterations in pica behavior and food intake resulting from the administration of ATR or DACT were reliably detected during this period.
Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, causes rapid increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To test whether administration of ATR causes hypothalamic–pituitary–adrenal (HPA) axis activation through the production of a generalized stress response resulting from gastrointestinal distress, we conducted both conditioned taste avoidance (CTA) and pica behavior experiments. Body temperature data were also collected to detect the presence of stress-induced hyperthermia. Adult male Wistar rats were given a single oral dose of ATR (0, 5, 25, 50, 100, or 200 mg/kg) or the primary ATR metabolite diamino-s-chlorotriazine (DACT; 135 mg/kg). Increases were observed in ACTH (LOEL, 12.5 mg/kg), CORT (LOEL, 5 mg/kg) and progesterone (LOEL, 5 mg/kg) 15 min following a single dose of ATR. DACT (135 mg/kg) increased ACTH (1.3-fold), CORT (2.9-fold) and progesterone (1.9-fold) above vehicle control concentrations, but the magnitude of the responses was much lower than that observed for an equal molar dose of ATR (200 mg/kg; 7.0, 9.0 and 11.0-fold above ACTH, CORT, progesterone controls, respectively). CTA results demonstrated conditioned taste avoidance to ATR, with a NOEL of 5 mg/kg. Animals dosed with DACT developed avoidance responses comparable to the highest dose of ATR. In the pica experiment, lower doses (5–50 mg/kg) of ATR had no effect on pica behavior, as measured 6 and 24 h post-dosing, nor did DACT. However, the highest dose of ATR (200 mg/kg) did induce pica behavior at both time points. No differences in body temperature were observed. Overall, results indicate that increases in ACTH and CORT secretion following administration of ATR occur at doses that are without effect on the display of pica behavior, indicating that the HPA-axis activation caused by ATR is not likely the result of gastrointestinal distress.
Endocrine, behavioral and autonomic effects of neuropeptide AF
2009, Hormones and Behavior
The actions of neuropeptide AF (NPAF), on the hypothalamic-pituitary-adrenal (HPA) axis, behavior and autonomic functions were investigated. NPAF (0.25, 0.5, 1, 2 nmol) was administered intracerebroventricularly to rats, the behavior of which was monitored by means of telemetry, open-field (OF) observations and elevated plus-maze (EPM) tests. The temperature and heart rate were recorded by telemetry, and the plasma ACTH and corticosterone levels were used as indices of the HPA activation. The dopamine release from striatal and amygdala slices after peptide treatment (100 nM and 1 μM) was measured with a superfusion apparatus. To establish the transmission of the HPA response, animals were pretreated with the corticotrophin-releasing hormone (CRH) receptor antagonist antalarmin or astressin 2B (0.5 nmol). In the OF test, the animals were pretreated with antalarmin or haloperidol (10 μg/kg), while in the EPM test they were pretreated with antalarmin or diazepam (1 mg/kg). NPAF stimulated ACTH and corticosterone release, which was inhibited by antalarmin. It activated exploratory locomotion (square crossings and rearings) and grooming in OF observations, and decreased the entries to and the time spent in the open arms during the EPM tests. The antagonists inhibited the locomotor responses, and also attenuated grooming and the EPM responses. NPAF also increased spontaneous locomotion, and tended to decrease the core temperature and the heart rate in telemetry, while it augmented the dopamine release from striatal and amygdala slices. These results demonstrate, that acute administration of exogenous NPAF stimulates the HPA axis and behavioral paradigms through CRH and dopamine release.
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The present experiments focused on the effects of neuromedin S on hypothalamic–pituitary–adrenal (HPA) activation and behavior. The peptide (0.25–1 nmol) was administered intracerebroventricularly to rats, the behavior of which was monitored by means of telemetry, open field observations and an elevated plus-maze (EPM) test. Autonomic functions such as the temperature and the heart rate were recorded by telemetry. The action on the HPA axis was assessed via measurements of the plasma corticosterone and ACTH levels. To reveal the transmission of the endocrine responses, animals were pretreated with corticotrophin releasing hormone receptor (CRHR) antagonists (1 nmol). In the open field test, the animals were pretreated with either a CRHR₁ antagonist (antalarmin) or haloperidol (10 μg/kg), while in the EPM test they were pretreated with antalarmin or diazepam (1 mg/kg). The dopamine release from striatal and amygdala slices after peptide treatment was measured with a superfusion apparatus. Neuromedin S exerted dose-dependent effects on the HPA system, which were inhibited by antalarmin. It also activated grooming and decreased the entries to and time spent in the open arms during the EPM test. The grooming response was abolished by haloperidol and antalarmin pretreatment, while diazepam and antalarmin showed a tendency to attenuate the response evoked in the EPM test. In the superfusion studies, neuromedin S enhanced the dopamine release from the amygdala slices. These results demonstrate that neuromedin S stimulates the HPA axis through the CRHR₁ pathway and evokes stereotyped behavior and anxiety through mesolimbic dopamine and corticotrophin releasing hormone release.

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Life Sciences

ICV-CRH potently affects behavior without altering antinociceptive responding

Abstract

Brain Res.

Brain Res.

Life Sci.

Brain Res.

Life Sci.

Pharmacol. Biochem. Behav.

Life Sci.

Life Sci.

Neurosci. Lett.

Pharm Biochem Behav

Science

Science

Anxiolytic effect of the GPR103 receptor agonist peptide P550 (homolog of neuropeptide 26RFa) in mice. Involvement of neurotransmitters

The actions of neuropeptide SF on the hypothalamic-pituitary-adrenal axis and behavior in rats

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

Atrazine does not induce pica behavior at doses that increase hypothalamic-pituitary-adrenal axis activation and cause conditioned taste avoidance

Endocrine, behavioral and autonomic effects of neuropeptide AF

Endocrine and behavioral effects of neuromedin S