Stress-induced sensitization of CRH-ir but not P-CREB-ir responsivity in the rat central nervous system.

There is some evidence that a traumatic life event can induce long-term alterations in corticotropin-releasing hormone (CRH) producing neurons in humans, which may play a role in the pathophysiology of anxiety disorders, including post-traumatic stress disorder (PTSD). To study the long-term effects of a traumatic event on brain CRH-immunoreactivity (CRH-ir) and phospho-cAMP response element binding protein-immunoreactivity (P-CREB-ir), rats were exposed to a single session of foot shocks (preshocked) or no shocks (control). Two weeks later half of the control rats and half of the preshocked rats received an electrified prod in the home cage for 15 min and behavior was recorded.

Effects of flesinoxan on corticosteroid receptor expression in the rat hippocampus.

Many agents that influence serotonergic neurotransmission modulate expression of hippocampal corticosteroid receptors. We have studied the effect of the specific 5-hydroxytryptamine, 5-HT(1A), receptor agonist flesinoxan on mRNA for glucocorticoid and mineralocorticoid receptors in the hippocampus and dorsal raphe nucleus. Since some responses to 5-HT(1A) receptor stimulation show a strong desensitization, we studied the effect of a single and repeated injections of flesinoxan.

Long-term sensitization of Fos-responsivity in the rat central nervous system after a single stressful experience.

There is considerable evidence for a role of stressful experiences in psychosomatic disorders in humans, but the mechanisms leading to altered responsivity and the relative contributions of central and peripheral neuronal changes, however, are still under debate. To investigate the contribution of specific brain areas to sensitized responsivity, rats were exposed to a single brief session of inescapable footshocks (preshocked) or no shocks (control) in a gridcage. Two weeks later, an electrified prod was inserted in the home cage for 15 min and the behaviour recorded.

Flesinoxan treatment reduces 5-HT1A receptor mRNA in the dentate gyrus independently of high plasma corticosterone levels.

Flesinoxan acts as a full 5-HT1A receptor agonist and displays anxiolytic and anti-depressant properties. 5-HT1A receptor agonists, including flesinoxan, increase corticosterone (B) levels in the blood and reduces 5-HT1A receptor mRNA expression in the hippocampus. In this study, we examined whether the 5-HT1A receptor downregulation induced by flesinoxan involves corticosterone control of 5-HT1A receptor gene transcription.

Flesinoxan pretreatment differentially affects corticosterone, prolactin and behavioural responses to a flesinoxan challenge.

To determine whether alterations in 5-HT1A receptor mediated responses induced by a single injection with a selective 5-HT1A receptor agonist is a transient effect, or whether the (de)sensitisation is more persistent, rats were pretreated with the selective and full 5-HT1A receptor agonist, flesinoxan (3 mg/kg SC once daily) for either 1 day or 1 week. Twenty-four hour after the last pretreatment injection, rats were challenged with flesinoxan (3 mg/kg SC), and the effects on plasma corticosterone and prolactin levels, lower lip retraction and behaviour in the shock-probe burying test were determined. Several 5-HT1A receptor mediated responses were modified differentially following the flesinoxan pretreatment.

Pretreatment with 5-HT1A receptor agonist flesinoxan attenuates Fos protein in rat hypothalamus.

The 5-HT1A receptor agonist flesinoxan has anxiolytic activity and concurrently enhances plasma corticosterone levels in rats. After a second injection of flesinoxan 24 h later, the corticosterone response disappears, but not the anxiolytic effects. Male rats received two injections with either flesinoxan or vehicle within 24 h.

5-HT1A receptor agonist flesinoxan enhances Fos immunoreactivity in rat central amygdala, bed nucleus of the stria terminalis and hypothalamus.

5-Hydroxytryptamine-1A (5-HT1A) receptor agonists, including flesinoxan, reduce anxiety and activate the hypothalamus-pituitary-adrenal (HPA) axis under basal conditions. In order to investigate the underlying neural mechanisms we investigated immunoreactivity for the immediate early gene protein product Fos (Fos-ir) in rat brains 1 h after flesinoxan treatment (0.0, 0.

Alterations in the immunoreactivity for muscarinic acetylcholine receptors and colocalized PKC gamma in mouse hippocampus induced by spatial discrimination learning.

This study describes changes in the immunoreactivity for muscarinic acetylcholine receptors (mAChRs) in the hippocampus of mice in relation to spatial discrimination behavior, employing the monoclonal antibody M35 raised against purified bovine mAChR protein. Performance in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes served as the measure of spatial discrimination learning and memory. Twenty-six adult male house mice were used, divided into four groups.

Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny.

Testosterone (T) and estradiol (E2) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behaviour via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E2, by the enzyme aromatase.

Aromatase activity in the preoptic area differs between aggressive and nonaggressive male house mice.

Treatment with testosterone (T) or estradiol (E2) facilitates intraspecific aggressive behavior in adult rodents. Brain aromatization of T to E2 appears to be involved in facilitation of fighting behavior. In the present study we measure the in vitro brain aromatase activity (AA) in the preoptic area (POA), amygdaloid nuclei (Am), ventromedial hypothalamus (VMH), and parietal cortex (CTX) from two strains of adult male house mice, which were genetically selected for territorial aggression, based upon their attack latencies (short attack latency: SAL; long attack latency: LAL).

Genetic differences in female house mice in aggressive response to sex steroid hormone treatment.

Male mice, genetically selected for aggression, characterized by short attack latency (SAL) or long attack latency (LAL), differ on several testosterone (T)-related parameters during ontogeny and adult age. The variation in aggressive behavior at adult age may be due to differences in degree of androgenization prenatally. When exposed to T at prenatal, neonatal, and/or adult age, nonlactating females also display intraspecific fighting behavior.

Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice.

The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL).

Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning.

In the present study, we examined changes in immunoreactivity (ir) for the gamma-isoform of protein kinase C (PKC gamma) in mouse hippocampus in relation to spatial memory processes employing the monoclonal antibody 36G9 raised against purified PKC gamma. Learning and memory were assessed by performance in a free-choice spatial pattern paradigm in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes. Adult male house mice were used, divided in four groups.

Differences in the number of arginine-vasopressin-immunoreactive neurons exist in the suprachiasmatic nuclei of house mice selected for differences in nest-building behavior.

Arginine-vasopressin (AVP) is a homeostatic modulator of body temperature during fever and may also be involved in normal body temperature control. In the present study the hypothalamus of mice bi-directionally selected for thermoregulatory nest-building behavior was immunocytochemically labeled for AVP. The low-selected mice had a 1.

Differential effects of neonatal testosterone treatment on aggression in two selection lines of mice.

Selection lines of mice, artificially selected for aggression based upon the attack latency score (ALS), were used. In order to determine the relative contribution of neonatal testosterone (T) in the development of aggression, we vary the plasma-T level in males of both selection lines on the day of birth. At 14 weeks the ALS was measured.

Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex.

The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the cholinergic fiber density in the cortex decreased by 66% with a concurrent increase in SOM-i fibers by more than 50% and a 124% increase in NPY-i fiber innervation. The neuropeptidergic sprouting response on cholinergic denervation does not match the concurrent cholinergic and peptidergic decline in Alzheimer's disease and as such does not support the cholinergic lesion alone as an animal model for this neurodegenerative disorder.