DIFFERENTIAL EFFECTS OF CRH INFUSION INTO THE CENTRAL NUCLEUS OF THE AMYGDALA IN THE ROMAN HIGH-AVOIDANCE AND LOW-AVOIDANCE RATS

https://doi.org/10.1016/S0306-4530(97)00098-XGet rights and content

Abstract

Roman-high (RHA/Verh) and low (RLA/Verh) avoidance rats are selected and bred for rapid learning versus non-acquisition of two-way, active avoidance behaviour in a shuttle box. RHA/Verh rats generally show a more active coping style than do their RLA/Verh counterparts when exposed to various environmental challenges. The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses to stress and stress-free conditions, and it is considered in relation to coping strategies. Corticotropin-releasing hormone (CRH) seems to be a key factor in the control of the CeA output. Neuroanatomical studies have revealed that the majority of CRH fibers from the CeA have direct connections with autonomic regulatory nuclei in the brainstem, e.g. lateral parabrachial nucleus (lPB), ventrolateral periaquaductal gray (vlPAG). The modulating effects of CRH (30 ng) on CeA activity were studied by infusion of CRH into the CeA in freely moving male RHA/Verh and RLA/Verh rats under stress-free conditions. Heart-rate and behavioural activities were repeatedly measured before, during and after local administration of CRH or vehicle, after which early gene product FOS immunocytochemistry and CRH-mRNA in situ hybridisation were carried out in selected brain areas. CRH infusion into the CeA caused a long lasting increase in heart-rate and behavioural activation in the RHA/Verh rats, leaving the RLA/Verh rats unaffected. As a result of CRH infusion, the number of FOS positive cells in the CeA and lPB of RLA/Verh rats was increased whereas an opposite response was found in the RHA/Verh rats. However, CRH into the CeA of the Roman rat lines induced no pronounced effects on FOS staining in the vlPAG and CRH mRNA levels in the CeA. These results indicate that the CRH system of the CeA, connected with the output brainstem areas, is differentially involved in cardiovascular and behavioural responses. © 1998 Elsevier Science Ltd. All rights reserved.

Section snippets

INTRODUCTION

Corticotropin-releasing hormone (CRH) is a neuropeptide that has been widely associated with several behavioural and physiological aspects of stress (Dunn and Berridge, 1990, Owens and Nemeroff, 1991). In addition to its activating effects on the hypothalamus–pituitary–adrenal axis, intracerebroventricular (icv) injection of CRH produces elevations of heart-rate and blood pressure, as well as rises in plasma catecholamine and glucose levels (Bakke et al., 1990, Brown et al., 1982, Brown and

Animals

Twenty-three RHA/Verh and 23 RLA/Verh (male, Wistar-derived) rats, weighing 280–380 g at the beginning of the experiment, were used. Animals were obtained from the breeding colony at the Animal Science Institute (Zurich, Switzerland) at the age of 5–8 weeks. The rats were housed in groups of five animals per cage and left undisturbed until the age of 14 weeks in a temperature controlled room (20±1°C) with a 12-h light–dark cycle (lights on from 0800 to 2000h). Three days before surgery the

Histology

Following histological examination, five out of the 46 animals used had to be excluded from further analysis because of improper bilateral cannula placement. The cannula tips had to be localised just above or entering the dorsal edge of the CeA.

Cardiac responses

Fig. 1 shows the change in heart-rate before, during and after infusion of 30 ng of CRH or aCSF into the CeA, compared with basal values of heart-rate (t=−10 and −1 min). No significant differences were found in basal heart-rate values of all the groups

DISCUSSION

The major finding of the present study is that local CRH microinfusion into the CeA of RHA/Verh and RLA/Verh rats resulted in distinctly different behavioural, physiological and neurobiological responses under stress-free conditions.

RHA/Verh rats responded to this treatment with an increase in heart-rate which lasted for at least 17 min. This was accompanied by decreased resting/sleeping indicating an increase in overall behavioral activation. The same treatment induced only a slight behavioral

Acknowledgements

The authors wish to thank Dr P. Driscoll for kindly providing the RHA/Verh and RLA/Verh rats. This study is financially supported by the Council of Geological and Biological Sciences of the Netherlands Organization for Scientific Research within the research program ‘Neuropeptides and Behaviour’, SLW-BION Grant no: 805-16-206.

References (48)

  • Andreae, L. C. and Herbert, J. (1993) Expression of c-fos in restricted areas of the basal forebrain and brainstem...
  • Aubry, J. M., Bartanusz, V., Driscoll, P., Schulz, P., Steimer, T. and Kiss, J. Z. (1995) Corticotropin-releasing...
  • Bakke, H. K., Bogsnes, A. and Murison, R. (1990) Studies on the interaction between icv effects of CRF and CNS...
  • Berridge, C. W. and Dunn, A. J. (1987) Corticotropin-releasing factor reverses the stress-induced changes of...
  • Bohus, B. (1974) Telemetred heart rate responses of the rat during free and learned behavior. Biotelemetry 1,...
  • Bohus, B., Benus, R. F., Fokkema, D. S., Koolhaas, J. M., Nyakas, C., van Oortmerssen, G. A., Prins, A. J. A., de...
  • Britton, D. R., Koob, G. F., Rivier, J. and Vale, W. (1982) Intraventricular corticotropin-releasing factor enhances...
  • Brown, M. R. and Fisher, L. A. (1985) Corticotropin-releasing factor: effects on the autonomic nervous system and...
  • Brown, M. R., Fisher, L. A., Spiess, J., Rivier, C., Rivier, J. and Vale, W. (1982) Corticotropin-releasing factor:...
  • Castanon, N., Dulluc, J., LeMoal, M. and Mormede, P. (1994) Maturation of the behavioral and neuroendocrine differences...
  • Castanon, N. and Mormede, P. (1994) Psychobiogenetics-Adapted tools for the study of the coupling between behavioral...
  • Castanon, N., Perezdiaz, F. and Mormede, P. (1995) Genetic analysis of the relationships between behavioral and...
  • D'Angio, M., Serrano, A., Driscoll, P. and Scatton, B. (1988) Stressful environmental stimuli increase extracellular...
  • Diamant, M. and De Wied, D. (1991) Autonomic and behavioral effects of centrally administered corticotropin-releasing...
  • Driscoll, P. and Battig, K. (1982) Behavioral, emotional and neurochemical profiles in rats selected for extreme...
  • Driscoll, P., Dedek, J., D'Angio, M., Claustre, Y. and Scatton, B. (1990) A genetically-based model for divergent...
  • Dunn, A. J. and Berridge, C. W. (1990) Physiological and behavioral responses to corticotropin-releasing factor...
  • Escorihuela, R. M., Tobena, A., Driscoll, P. and Fernandezteruel, A. (1995) Effects of training, early handling, and...
  • Ferre, P., Fernandezteruel, A., Escorihuela, R. M., Driscoll, P., Corda, M. G., Giorgi, O. and Tobena, A. (1995)...
  • Fisher, L. A. (1988) Corticotropin-releasing factor: central nervous system effects on baroreflex control of heart...
  • Fisher, L. A. and Brown, M. R. (1991) Central regulation of stress responses: regulation of the autonomic nervous...
  • Fisher, L. A., Jessen, G. and Brown, M. R. (1983) Corticotropin-releasing factor (CRF): mechanism to elevate mean...
  • Gentsch, C., Lichtsteiner, M., Driscoll, P. and Feer, H. (1982) Differential hormonal and physiological responses to...
  • Gentsch, C., Lichtsteiner, M. and Feer, H. (1981) Locomotor activity, defecation score and corticosterone levels during...
  • Cited by (22)

    • High-sugar/high-fat diet modulates the effects of chronic stress in cariocas high- and low-conditioned freezing rats

      2022, Physiology and Behavior
      Citation Excerpt :

      During sustained fear, CRH release is mediated by stimulation of the bed nucleus of the stria terminalis through basolateral amygdala projections. In turn, this increase in CRH levels triggers a positive feedback via activation of the central amygdala and the periaqueductal gray, potentiating fear responses, such as startle [17,39,69,71]. Previous findings from our group have demonstrated that the amygdala plays a critical role in the fear responses of CHF animals [24].

    • Density of acetylcholine esterase (AchE) and tyrosine hydroxylase (TH) containing fibers in the amygdala of roman high- and low-avoidance rats

      2016, Neuroscience Letters
      Citation Excerpt :

      Thus, the higher density of TH-ir fibers in RLA rats correlates well with an increased number of Ce-CRH neurons in this line compared to RHA rats [47]. Because Ce-CRH neurons regulate stress-related arousal and fear conditioning [33], the higher number of CRH neurons [6,44,47] is compatible with an enhanced stress responsivity of RLA rats [40]. Moreover, CRH-containing Ce neurons, mostly localized in the CeL, provide both inhibitory and excitatory information to other Ce neurons [33], and project to downstream brain areas, through which they regulate behavioral (e.g., freezing, startle respose), autonomic (cardiovascular, skin conductance), and endocrine responses (e.g., glucocorticoid release) to stress- and fear-inducing stimuli [15,20,25,32,36].

    • Opposite effects of oxytocin and vasopressin on the emotional expression of the fear response

      2008, Progress in Brain Research
      Citation Excerpt :

      While it is possible that these different behavioural phenotypes are directly related to changes in vasopressin and oxytocin signalling in the CeA, other modulating factors may also be involved. For example, in RHA and RLA rats, the CRF system of the CeA appears to differentially affect cardiovascular and behavioural responses (Wiersma et al., 1998) and RLA rats have significantly more CRF neurons in the CeA than RHA rats (Yilmazer-Hanke et al., 2002). Interestingly, maternal care has been shown to both affect oxytocin and vasopressin receptor expression as well as anxiety and fear behaviour in adulthood, pointing further to a causal relation between behaviour and neuropeptidergic signalling (Francis et al., 2002).

    • Corticotropin-releasing hormone receptors in the medial prefrontal cortex regulate hypothalamic-pituitary-adrenal activity and anxiety-related behavior regardless of prior stress experience

      2007, Brain Research
      Citation Excerpt :

      We injected CRH (20 ng, 200 ng) or vehicle into the mPFC 30 min prior to testing. The selection of these doses was based on previous studies from our laboratory that injected CRH into the basolateral amygdala to examine behavior in the EPM and from others who have injected similar doses of CRH into the amygdala and examined behavioral activation and grooming in an open field (Wiersma et al., 1998; Daniels et al., 2004). We found that 20 ng of CRH decreased the number of open arm entries (0.3 ± 0.2) compared to vehicle (2.8 ± 1.2) as well as the time spent in the open arms (2.7 sec ± 1.2) compared to vehicle (29.6 sec ± 10.7).

    View all citing articles on Scopus
    View full text