Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF)

doi:10.1016/0031-9384(93)90230-D

Physiology & Behavior

Volume 54, Issue 3, September 1993, Pages 423-431

https://doi.org/10.1016/0031-9384(93)90230-D Get rights and content

Abstract

Wistar rats were kindled electrically in the anterior or posterior medial amygdala of the right hemisphere. One week after the fourth stage 5 seizure, anxiety was assessed in the elevated plus maze test. Anxiety levels of rats kindled in posterior medial amygdala were reduced relative to implanted controls, but not relative to unoperated controls. Kindling of the anterior medial amygdala increased anxiety relative to implanted and unoperated controls. The different effects of kindling on behavior were unrelated to any parameter of kindling. The stress of an ICV injection of saline increased anxiety in unkindled controls but reduced anxiety in anterior medial amygdala-kindled rats. Injection stress effects on behavior were blocked by 50 μg of α-helical CRF (the CRF receptor blocker). These findings suggest that CRF released by the stress of the injection procedure mediates the behavioral effects in both kindled and control rats. In contrast, injection of CRF (2 μg, ICV) has no greater effect than ICV saline in anterior medial amygdala kindled rats, whereas it was anxiogenic in unkindled rats. ICV vehicle and CRF reduce kindling-induced anxiety equally. These findings suggest that CRF released during the injection procedure saturates available CRF receptors. Finally, kindling did not alter basal plasma corticosterone levels. These and other findings suggest that the anxiety-modulating actions of CRF are at central CRF receptors.

References (33)

R. Adamec et al.
Partial kindling and emotional bias in the cat: Lasting after-effects of partial kindling of ventral hippocampus. I: Behavioral changes
Behav. Neural Biol.
(1983)
R. Adamec et al.
Partial kindling and emotional bias in the cat: Lasting after-effects of partial kindling of ventral hippocampus. II: Physiological changes
Behav. Neural Biol.
(1983)
R. Adamec
Does kindling model anything clinically relevant?
Biol. Psychiatry
(1990)
R.E. Adamec
Partial kindling of the ventral hippocampus: Identification of changes in limbic physiology which accompany changes in feline aggression and defense
Physiol. Behav.
(1991)
P.W. Gean et al.
Spontaneous epileptiform activity and alteration of GABA- and of NMDA-mediated neurotransmission in amygdala neurons kindled in vivo
Brain Res.
(1989)
T.R. Insel et al.
Central administration of corticotropin releasing factor alters rat pup isolation calls
Pharmacol. Biochem. Behav.
(1989)
E.D. Kemble et al.
Effect of regional amygdaloid lesions on flight and defensive behaviours of wild black-rats (Rattus rattus)
Physiol. Behav.
(1990)
M.J. Meaney et al.
Postnatal handling attenuates certain neuroendocrine, anatomical and cognitive dysfunctions associated with aging in female rats
Neurobiol. Aging
(1991)
S.A. Nieminen et al.
Amygdala kindling increased fear-response, but did not impair spatial memory in rats
Physiol. Behav.
(1992)
M.A. Smith et al.
Effects of amygdala kindling and electroconvulsive seizures on the expression of corticotropin releasing hormone mRNA in the rat brain
Mol. Cell Neurosci.
(1991)

A. Tazi et al.

Corticotropin-releasing factor antagonist blocks stress-induced fighting in rats

Regul. Pept.

(1987)

S.R.B. Weiss et al.

CRF-induced seizures and behavior: Interaction with amygdala kindling

Brain Res.

(1986)

J.T. Winslow et al.

CRH and α-helical-CRH modulate behavioral measures of arousal in monkeys

Pharmacol. Biochem. Behav.

(1989)

R. Adamec

Normal and abnormal limbic system mechanisms of emotive biasing

R. Adamec et al.

Limbic kindling and animal behavior—Implications for human psychopathology associated with complex partial seizures

Biol. Psychiatry

(1983)

R. Adamec

Kindling, anxiety and limbic epilepsy: Human and animal perspectives

Cited by (55)

The parental brain and behavior: A target for endocrine disruption
2019, Frontiers in Neuroendocrinology
During pregnancy, the sequential release of progesterone, 17β-estradiol, prolactin, oxytocin and placental lactogens reorganize the female brain. Brain structures such as the medial preoptic area, the bed nucleus of the stria terminalis and the motivation network including the ventral tegmental area and the nucleus accumbens are reorganized by this specific hormonal schedule such that the future mother will be ready to provide appropriate care for her offspring right at parturition. Any disruption to this hormone pattern, notably by exposures to endocrine disrupting chemicals (EDC), is therefore likely to affect the maternal brain and result in maladaptive maternal behavior. Development effects of EDCs have been the focus of intense study, but relatively little is known about how the maternal brain and behavior are affected by EDCs. We encourage further research to better understand how the physiological hormone sequence prepares the mother’s brain and how EDC exposure could disturb this reorganization.
Repeatedly stressed rats have enhanced vulnerability to amygdala kindling epileptogenesis
2013, Psychoneuroendocrinology
Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n = 18) or non-stressed (n = 19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced (‘the fully kindled state’). Stressed rats were exposed to 30 min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122 ± 17 ng/ml; post-stress: 632 ± 33 ng/ml), with no habituation observed over the experiment. Stressed rats reached the ‘fully kindled state’ in significantly fewer stimulations than non-stressed rats (21 ± 1 vs 33 ± 3 stimulations; p = 0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p < 0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans.
Central CRH administration changes formalin pain responses in male and female rats
2011, Brain Research
Citation Excerpt :
Under stressful conditions, CRH increases sensitivity and reactivity to aversive stimulation (Dunn and Berridge, 1990; Adamec and McKay, 1993; Koob et al., 1993); for instance, CRH administration increases the time spent freezing or shock-induced fighting (Dunn and Berridge, 1990; Koob et al., 1993; Menzaghi et al., 1993). The behavioral effects of CRH can be independent of HPA axis activation (Adamec and McKay, 1993; Menzaghi et al., 1993), showing that CRH can mediate the responses to stressors both via the HPA axis and independently of the HPA axis (De Souza, 1995; Adamec and McKay, 1993). The role of CRH in pain and analgesia has been neglected until recently (Lariviere and Melzack, 2000).
Corticotropin-releasing hormone (CRH) is suggested to be involved in the regulation of pain. To better evaluate the CRH-mediated behavioral alterations in the formalin inflammatory pain test, we administered CRH or the CRH receptor antagonist α-helical CRH_9–41 (ahCRH) intracerebroventricularly to male and female rats and compared the effects with those of saline control. Nociceptive stimulation was carried out through a subcutaneous injection of dilute formalin (50 μL, 10%) in the plantar surface of the hind paw. In both sexes, formalin-induced responses, recorded for 60 min, were affected by CRH but not by ahCRH treatment. Paw flexing duration was decreased in both sexes during the formalin interphase period in the CRH-treated group compared to saline control groups; however, licking of the injected paw was markedly increased by the same treatment at other time periods. Treatments induced only a few changes in spontaneous non-pain behaviors, which do not account for the effects on pain response. In conclusion, these data demonstrate the ability of CRH to affect the behavioral responses to an inflammatory nociceptive stimulus, and that the effects can be in opposite directions depending on the behavioral response considered.
Amygdaloid kindling is anxiogenic but fails to alter object recognition or spatial working memory in rats
2008, Epilepsy and Behavior
Kindling in rats produces enduring behavioral changes that parallel the psychobehavioral disturbances frequently accompanying temporal lobe epilepsy. Some evidence suggests that the site of kindling is an important determinant of the type of behavioral changes observed following kindling, although this variable has not been systematically investigated. In the present experiments, the effects of amygdaloid kindling were assessed on a battery of behavioral tests we used previously to assess the effects of kindling in dorsal hippocampus or perirhinal cortex. Three generalized seizures were kindled with stimulation in or near the basolateral amygdala. One week later, rats were tested successively on measures of anxiety, activity, object recognition memory, and spatial working memory over a period of 3 weeks. Amygdaloid kindling produced increased anxiety, but spared all other behaviors assessed. This pattern of results is partially distinct from the previously described effects of perirhinal cortical kindling, which increases anxiety but also impairs object recognition memory, and is completely distinct from dorsal hippocampal kindling, which selectively increases activity and impairs spatial working memory. The observations suggest that kindling of distinct highly interconnected temporal lobe sites produces distinct patterns of behavioral comorbidity. The underlying mechanisms are thus most likely localized to intrinsic circuits at the site of seizure origination.
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
The hypothalamic–pituitary–adrenal (HPA) axis habituates, or gradually decreases its activity, with repeated exposure to the same stressor. During habituation, the HPA axis likely requires input from cortical and limbic regions involved in the processing of cognitive information that is important in coping to stress. Brain regions such as the medial prefrontal cortex (mPFC) are recognized as important in mediating these processes. The mPFC modulates stress-related behavior and some evidence suggests that the mPFC regulates acute and repeated stress-induced HPA responses. Interestingly, corticotropin-releasing hormone (CRH)-1 receptors, which integrate neuroendocrine, behavioral and autonomic responses to stress, are localized in the mPFC but have not been specifically examined with respect to HPA regulation. We hypothesized that CRH receptor activity in the mPFC contributes to stress-induced regulation of HPA activity and anxiety-related behavior and that CRH release in the mPFC may differentially regulate HPA responses in acutely compared to repeatedly stressed animals. In the present experiments, we found that blockade of CRH receptors in the mPFC with the non-selective receptor antagonist d-Phe-CRH (50 ng or 100 ng) significantly inhibited HPA responses compared to vehicle regardless of whether animals were exposed to a single, acute 30 min restraint or to the eighth 30 min restraint. We also found that intra-mPFC injections of CRH (20 ng) significantly increased anxiety-related behavior in the elevated plus maze in both acutely and repeatedly restrained groups compared to vehicle. Together, these results suggest an excitatory influence of CRH in the mPFC on stress-induced HPA activity and anxiety-related behavior regardless of prior stress experience.
Dendritic spines in the posterodorsal medial amygdala after restraint stress and ageing in rats
2007, Neuroscience Letters
Several evidences suggest that the posterodorsal medial amygdala (MePD) can be a relevant part of the rat neural circuitry for the regulation of hypothalamic neuroendocrine secretion and for ontogenetically different behavioral displays. The dendritic spine density of Golgi-impregnated neurons from the MePD was evaluated in young rats following acute or chronic restraint stress and in aged animals (24 months old). Compared to the control group, a single 1 h restraint stress session promoted a decreased spine density (p < 0.01) whereas a single 6 h restraint stress session or daily 6-h restraint sessions for 28 consecutive days did not lead to the same effect (p > 0.05). Aged rats showed no difference in this dendritic spine parameter when compared to young adults (p > 0.05). These results indicate that short-term stress (1 h) can affect MePD dendritic spines and that neural plasticity is involved with adaptive responses onwards in restrained rats. On the other hand, brain structural modifications related with ageing appear not to influence the number of certain postsynaptic sites in the MePD of rats.

View all citing articles on Scopus

View full text

ArticleAmygdala kindling, anxiety, and corticotrophin releasing factor (CRF)

Abstract

Behav. Neural Biol.

Behav. Neural Biol.

Biol. Psychiatry

Physiol. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Physiol. Behav.

Neurobiol. Aging

Physiol. Behav.

Mol. Cell Neurosci.

Regul. Pept.

Brain Res.

Pharmacol. Biochem. Behav.

Normal and abnormal limbic system mechanisms of emotive biasing

Limbic kindling and animal behavior—Implications for human psychopathology associated with complex partial seizures

Biol. Psychiatry

Kindling, anxiety and limbic epilepsy: Human and animal perspectives

Article
Amygdala kindling, anxiety, and corticotrophin releasing factor (CRF)