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Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but their receptor localization has not. This is the first combination of a light microscopic and ultrastructural study to localize corticotropin-releasing factor receptors immunohistologically in the developing rat cerebellum. Both CRF-R1 and CRF-R2 were expressed in climbing fibres from early stages (post-natal day 3) to the adult, but CRF-R2 immmunoreactivity was only prominent throughout the molecular layer in the posterior cerebellar lobules. CRF-R1 immunoreactivity was concentrated in apical regions of Purkinje cell somata and later in primary dendrites exhibiting a diffuse cytoplasmic appearance. In Purkinje cells, CRF-R1 immunoreactivity was never membrane bound post-synaptically in dendritic spines while CRF-R2 immunoreactivity was found on plasmic membranes of Purkinje cells from post-natal day 15 onwards. We conclude that the localization of these receptors in cerebellar afferents implies their pre-synaptic control of the release of corticotropin-releasing factor-like ligands, impacting on the sensory information being transmitted from afferents. Furthermore, the fact that CRF-R2 is membrane bound at synapses, while CRF-R1 is not, suggests that ligands couple to CRF-R2 via synaptic transmission and to CRF-R1 via volume transmission. Finally, the distinct expression profiles of receptors along structural domains of Purkinje cells suggest that the role for these receptors is to modulate afferent inputs.

The inhibitory avoidance paradigm allows the study of mechanisms underlying learning and memory formation in zebrafish (Danio rerio Hamilton). For zebrafish, the physiology and behavior associated with this paradigm are as yet poorly understood. We therefore assessed the effects of environmental enrichment and fish age on inhibitory avoidance learning. Fish raised in an environmentally enriched tank showed decreased anxiety-like behavior and increased exploration. Enrichment greatly reduced inhibitory avoidance in 6-month (6M)- and 12-month (12 M)-old fish. Following inhibitory avoidance, telencephalic mRNA levels of proliferating cell nuclear antigen (pcna), neurogenic differentiation (neurod), cocaine- and amphetamine-regulated transcript 4 (cart4), and cannabinoid receptor 1 (cnr1) were lower in enriched-housed fish, while the ratios of mineralocorticoid receptor (nr3c2)/glucocorticoid receptor α [nr3c1(α)] and glucocorticoid receptor β [nr3c1(β)]/glucocorticoid receptor α [nr3c1(α)] were higher. This was observed for 6M-old fish only, not for 24-month (24 M) old fish. Instead, 24 M-old fish showed delayed inhibitory avoidance, no effects of enrichment, and reduced expression of neuroplasticity genes. Overall, our data show strong differences in inhibitory avoidance behavior between zebrafish of different ages and a clear reduction in avoidance behavior following housing under environmental enrichment.

Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive burying response, the effects of an ICV CRF antagonist were tested on defensive burying behaviors as well as the plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone response. Rats were allowed to self-administer one mild electric shock (1.0 mA) through a probe mounted on the wall of the home cage by briefly touching it. Following this shock, control rats typically display burying behavior, as defined as moving the bedding material toward and/or over the shock probe. A CRF antagonist, alpha-he1 CRF(9-41), was administered ICV (1, 5, and 25 mu g) 1 min after they received the shock. The 5 mu g dose of the CRF antagonist significantly attenuated the time spent in defensive burying compared to vehicle-treated controls. The 5 and 25 mu g doses of alpha-he1 CRF(9-41) increased the latency to display defensive burying. However, the enhanced release of plasma ACTH and plasma corticosterone concentrations in the stressed animals was not significantly modified over the 15-min period by either of the three doses of CRF antagonist. The results suggest that endogenous CRF is involved in the expression of defensive burying behavior and that the brain CRF receptors modulating the behavioral response may be different from the CRF receptors modulating the hormonal response of defensive burying.

Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive burying response, the effects of an ICV CRF antagonist were tested on defensive burying behaviors as well as the plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone response. Rats were allowed to self-administer one mild electric shock (1.0 mA) through a probe mounted on the wall of the home cage by briefly touching it. Following this shock, control rats typically display burying behavior, as defined as moving the bedding material toward and/or over the shock probe. A CRF antagonist, alpha-hel CRF9-41, was administered ICV (1, 5, and 25 micrograms) 1 min after they received the shock. The 5 micrograms dose of the CRF antagonist significantly attenuated the time spent in defensive burying compared to vehicle-treated controls. The 5 and 25 micrograms doses of alpha-hel CRF9-41 increased the latency to display defensive burying. However, the enhanced release of plasma ACTH and plasma corticosterone concentrations in the stressed animals was not significantly modified over the 15-min period by either of the three doses of CRF antagonist. The results suggest that endogenous CRF is involved in the expression of defensive burying behavior and that the brain CRF receptors modulating the behavioral response may be different from the CRF receptors modulating the hormonal response of defensive burying.

Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive burying response, the effects of an ICV CRF antagonist were tested on defensive burying behaviors as well as the plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone response. Rats were allowed to self-administer one mild electric shock (1.0 mA) through a probe mounted on the wall of the home cage by briefly touching it. Following this shock, control rats typically display burying behavior, as defined as moving the bedding material toward and/or over the shock probe. A CRF antagonist, alpha-he1 CRF(9-41), was administered ICV (1, 5, and 25 mu g) 1 min after they received the shock. The 5 mu g dose of the CRF antagonist significantly attenuated the time spent in defensive burying compared to vehicle-treated controls. The 5 and 25 mu g doses of alpha-he1 CRF(9-41) increased the latency to display defensive burying. However, the enhanced release of plasma ACTH and plasma corticosterone concentrations in the stressed animals was not significantly modified over the 15-min period by either of the three doses of CRF antagonist. The results suggest that endogenous CRF is involved in the expression of defensive burying behavior and that the brain CRF receptors modulating the behavioral response may be different from the CRF receptors modulating the hormonal response of defensive burying.

The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of the CRH fibres from the CeA have direct connections with autonomic regulatory nuclei in the brainstem. In the present study, the effects of locally infused CRH (30 ng) into the CeA, in freely moving male Wistar rats under stress-free conditions, were examined. Heart rate, endocrine parameters and behavioural activity were repeatedly measured before, during and after local administration of CRH, pretreated with either artificial CSF or the CRH-receptor antagonist, alpha-helical CRH (alpha-hCRH). CRH infusion alone caused a long-lasting increase in heart rate without affecting plasma adrenaline and noradrenaline as indicators of sympathetic activity. This CRH-induced tachycardia was effectively blocked by pretreatment with a high dose (1 microgram) alpha-hCRH locally into the CeA, while the pretreatment with low dose (0.1 microgram) of the alpha-hCRH caused a minor blockade of the CRH-induced tachycardia. The results suggest that CRH mechanisms in the CeA regulate the autonomic changes probably only by affecting parasympathetic but not sympathetic output systems. Because CRH is given at the level of the cell body of the CRH neurons in the CeA, we suggest that the reduction of the parasympathetic output may be explained as an autoreceptor-mediated inhibition of CRH neurons from the CeA with parasympathetic-regulating brainstem nuclei.

The effects of intrahypothalamic administration of norfenfluramine (NFFL), an anorectic agent that increases serotonergic transmission, on plasma concentrations of glucose, free fatty acids (FFA), and their regulating hormones were investigated in resting and exercising rats. Infusion of 5 micrograms NFFL in 0.125 microliter aCSF/min into the nucleus paraventricularis of the hypothalamus (PVN) caused a significant increase of blood glucose, plasma epinephrine (E), and corticosterone concentrations. Plasma levels of FFA, insulin, or norepinephrine (NE) remained unchanged. Lower doses of NFFL (0.5 and 0.05 microgram/min) did not affect peripheral metabolism. The effects of NFFL in the PVN were completely prevented by prior administration of a 5-HT1 antagonist, (S)-(-)propranolol. The exercise-induced increase of plasma NE was reduced after prior administration of 5 micrograms NFFL/min into the PVN. Plasma E responses tended to be increased. The exercise-induced alterations in glucose, FFA, corticosterone, and insulin were not affected by NFFL infusion into the PVN. The data suggest that activation of serotonergic mechanisms in the PVN might change the neurohormonal response to a stressor favouring the release of adrenal hormones above activation of the neuronal branch of the sympathetic nervous system.