Modulation of social learning in rats by brain corticotropin-releasing factor

Heinrichs, Stephen C.

doi:10.1016/j.brainres.2003.09.028

Cited by 30 publications

(29 citation statements)

References 49 publications

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“…For example, CRF has been shown to increase hippocampal long-term potentiation (Blank et al 2002;Wang et al 1998Wang et al , 2000 and facilitate learning of certain behavioral tasks, including aversive learning (Blank et al 2002;Garcia-Lecumberri and Ambrosio 2000;Heinrichs et al 1997b;Hung et al 1992;Lee 1995;Lee and Sung 1989;Liang et al 2001;Liang and Lee 1988;Ma et al 1999;Radulovic et al 1999;Zorrilla et al 2002), while disruption of CRF receptor function can attenuate certain forms of learning (Contarino et al 1999;Heinrichs 2003). Thus, the apparent blockade of intra-BNST CRF-induced conditioned place aversion by both CRF 1 and CRF 2 antagonist could be a result of an attenuated ability of the animal to associate the aversive effects of CRF in the BNST with the environment in which CRF is administered, rather than an attenuation of the actual aversive effects of CRF itself.…”

Section: Discussionmentioning

confidence: 99%

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

et al. 2006

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Rationale-Corticotropin releasing factor (CRF) produces anxiety-like and aversive effects when infused directly into the various regions of the brain, including the bed nucleus of the stria terminalis (BNST). However, the CRF receptor subtypes within the BNST mediating these phenomena have not been established.Objectives-We used selective CRF receptor antagonists to determine the receptor subtypes involved in the anxiogenic-like and aversive effects CRF in the BNST. Methods-MaleLong-Evans rats were bilaterally infused with CRF (0.2 or 1.0 nmol) either alone or in combination with the CRF 1 receptor antagonist CP154,526 or the CRF 2 receptor antagonist anti-sauvagine 30 (AS30) prior to behavioral testing in the elevated plus maze or place conditioning paradigms.Results-Intra-BNST administration of CRF produced a dose-dependent reduction in open arm entries and open arm time in the elevated plus maze, indicating an anxiogenic-like effect. These effects were inhibited by co-infusion of CP154,526 but not AS30, indicating that the anxiogeniclike effects of CRF in the BNST are mediated by CRF 1 receptors. Place conditioning with intra-BNST administration of CRF produced a dose-dependent aversion to the CRF-paired environment that was prevented by co-infusion of either CP154,526 or AS30, indicating that both CRF receptor subtypes mediate the aversive effects of this peptide. Intra-BNST infusions of the CRF receptor antagonists alone produced no effects in either behavioral paradigm.Conclusions-CRF 1 receptors in the BNST mediate the anxiogenic-like effects CRF in this region, whereas both CRF 1 and CRF 2 receptor subtypes mediate the conditioned aversive effects of this peptide within the BNST.

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Section: Discussionmentioning

confidence: 99%

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

et al. 2006

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“…Along these lines, UCN2 increases spontaneous parental behavior in prairie voles (Samuel et al, 2008). Evidence for an involvement of the CRH system in the modulation of social memory has been demonstrated by Heinrichs (2003) using CRH-R agonists and antagonists. To further elucidate the role of the CRH system in social behavior, we studied the social discrimination performance of UCN3, CRH-R2, and UCN2 knock-out mice.…”

Section: The Role Of Ucn3 In Social Behaviormentioning

confidence: 99%

Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2

Deussing

Breu

Kühne

et al. 2010

Journal of Neuroscience

117

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Urocortin 3 (UCN3) is strongly expressed in specific nuclei of the rodent brain, at sites distinct from those expressing urocortin 1 and urocortin 2, the other endogenous ligands of corticotropin-releasing hormone receptor type 2 (CRH-R2). To determine the physiological role of UCN3, we generated UCN3-deficient mice, in which the UCN3 open reading frame was replaced by a tau-lacZ reporter gene. By means of this reporter gene, the nucleus parabrachialis and the premammillary nucleus were identified as previously unknown sites of UCN3 expression. Additionally, the introduced reporter gene enabled the visualization of axonal projections of UCN3-expressing neurons from the superior paraolivary nucleus to the inferior colliculus and from the posterodorsal part of the medial amygdala to the principal nucleus of the bed nucleus of the stria terminalis, respectively. The examination of tau-lacZ reporter gene activity throughout the brain underscored a predominant expression of UCN3 in nuclei functionally connected to the accessory olfactory system. Male and female mice were comprehensively phenotyped but none of the applied tests provided indications for a role of UCN3 in the context of hypothalamic-pituitary-adrenocortical axis regulation, anxiety-or depression-related behavior. However, inspired by the prevalent expression throughout the accessory olfactory system, we identified alterations in social discrimination abilities of male and female UCN3 knock-out mice that were also present in male CRH-R2 knock-out mice. In conclusion, our results suggest a novel role for UCN3 and CRH-R2 related to the processing of social cues and to the establishment of social memories.

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“…‫,ء‬ p Ͻ 0.05 compared with a difference score of zero. [Panels A and B modified with permission from Heinrichs, 2003.] Panel C, CRF transgenic mice fail to perform an aversively motivated shuttle avoidance task as shown by mean ϩ S.E.M.…”

Section: Crf and Affective Regulation Learning And Memory Modulation:mentioning

confidence: 99%

Corticotropin-Releasing Factor in Brain: A Role in Activation, Arousal, and Affect Regulation

Heinrichs

Koob²

2004

J Pharmacol Exp Ther

Self Cite

323

223

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Organisms exposed to challenging stimuli that alter the status quo inside or outside of the body are required for survival purposes to generate appropriate coping responses that counteract departures from homeostasis. Identification of an executive control mechanism within the brain capable of coordinating the multitude of endocrine, physiological, and functional coping responses has high utility for understanding the response of the organism to stressor exposure under normal or pathological conditions. The corticotropin-releasing factor (CRF)/urocortin family of neuropeptides and receptors constitutes an affective regulatory system due to the integral role it plays in controlling neural substrates of arousal, emotionality, and aversive processes. In particular, available evidence from pharmacological intervention in multiple species and phenotyping of mutant mice shows that CRF/urocortin systems mediate motor and psychic activation, stimulus avoidance, and threat recognition responses to aversive stimulus exposure. It is suggested that affective regulation is exerted by CRF/urocortin systems within the brain based upon the sensitivity of local brain sites to CRF/urocortin ligand administration and the appearance of hypothalamo-pituitary-adrenocortical activation following stressor exposure. Moreover, these same stress neuropeptides may constitute a mechanism for learning to avoid noxious stimuli by facilitating the formation of so-called emotional memories. A conceptual framework is provided for extrapolation of animal model findings to humans and for viewing CRF/urocortin activation as a continuum measure linking normal and pathological states.Many experimental studies performed in animals support the role of corticotropin-releasing factor (CRF) peptides and receptors as mediators of interoceptive coping reactions to environmental or physiological challenges; however, the advent of small molecule ligands for CRF receptors suitable for administration in human beings raises the question of what insights, if any, anti-stress pharmacology exerted via CRF manipulations in animals provides for human biology and psychopathology. The present review addresses how the evidence for the adaptive utility of CRF systems provides a basis for predicting the consequences of brain CRF system activation or deactivation in man. The thesis most strongly supported by the available experimental evidence is that: 1) activating, 2) avoidant, and 3) learning/memory functions of CRF systems have evolved to serve affective regulatory needs in man and animals. The term affective can be defined as "relating to, arising from, or influencing feelings or emotions" (Webster's Ninth Collegiate Dictionary) whereas the related phrase affective disorder describes a disturbance of mood where mood is defined as a prolonged emotion that colors the whole psychic life (American Psychiatric Association, 1994). The reader familiar with the term homeostasis may be interested in one testable postulate that a certain environmental stimulus intensity...

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Modulation of social learning in rats by brain corticotropin-releasing factor

Cited by 30 publications

References 49 publications

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2

Corticotropin-Releasing Factor in Brain: A Role in Activation, Arousal, and Affect Regulation

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