Neuropeptide Y, calcitonin gene-related peptide, and neurokinin A in brain regions of HAB rats correlate with anxiety-like behaviours.

Anxiety disorders are pervasive psychiatric disorders causing great suffering. The high (HAB) and low (LAB) anxiety-related behaviour rats were selectively bred to investigate neurobiological correlates of anxiety. We compared the level of neuropeptides relevant for anxiety- and depression-related behaviours in selected brain regions of HAB and LAB rats.

CGRP in a gene-environment interaction model for depression: effects of antidepressant treatment.

Objective: Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored.

Sex-dependent behavior, neuropeptide profile and antidepressant response in rat model of depression.

A plethora of animal models of depression is described in the literature, aiming at mimicking different aspects of depression. Understanding the link between depression and stress has been and remains a major focus area for development of animal models, but lines of research with a more mechanistic focus targeting deficiencies in neurotransmitter systems or dysfunctional neuronal circuitries and neuroinflammation are also pursued vigorously. The main objectives of the present study were systematically to evaluate strain and sex characteristics of a genetic animal model, the Flinders Sensitive Line (FSL)/ Flinders Resistant Line (FRL), by applying behavioral, molecular and pharmacological measures relevant to depression, and compare it with the outbred Sprague Dawley rat.

Nortriptyline influences protein pathways involved in carbohydrate metabolism and actin-related processes in a rat gene-environment model of depression.

Although most available antidepressants increase monoaminergic neurotransmission, their therapeutic efficacy is likely mediated by longer-term molecular adaptations. To investigate the molecular changes induced by chronic antidepressant treatment we analysed proteomic changes in rat pre-frontal/frontal cortex and hippocampus after nortriptyline (NT) administration. A wide-scale analysis of protein expression was performed on the Flinders Sensitive Line (FSL), a genetically-selected rat model of depression, and the control Flinders Resistant Line (FRL).

Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression.

Stress has been shown to interact with genetic vulnerability in pathogenesis of psychiatric disorders. Here we investigated the outcome of interaction between genetic vulnerability and early-life stress, by employing a rodent model that combines an inherited trait of vulnerability in Flinders Sensitive Line (FSL) rats, with early-life stress (maternal separation). Basal differences in synaptic signaling between FSL rats and their controls were studied, as well as the consequences of early-life stress in adulthood, and their response to chronic antidepressant treatment (escitalopram).

CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls.

The purpose of this study was to examine the differential effects of acute tryptophan (TRP) depletion vs. sham condition on plasma, cerebrospinal fluid (CSF) biochemical parameters, and mood in the following three subject groups: (1) nine antidepressant-free individuals with remitted depression, (2) eight paroxetine-treated individuals with recently remitted depression, and (3) seven healthy controls. Plasma TRP decreased during TRP depletion and increased during sham condition (p<.

Increased levels of cocaine and amphetamine regulated transcript in two animal models of depression and anxiety.

The neurobiological bases of mood disorders remain elusive but both monoamines and neuropeptides may play important roles. The neuropeptide cocaine and amphetamine regulated transcript (CART) was shown to induce anxiety-like behavior in rodents, and mutations in the human CART gene are associated with depression and anxiety. We measured CART-like immunoreactivity (-LI) in genetic rat models of depression and anxiety, i.

Nortriptyline mediates behavioral effects without affecting hippocampal cytogenesis in a genetic rat depression model.

A prevailing hypothesis is that neurogenesis is reduced in depression and that the common mechanism for antidepressant treatments is to increase it in adult hippocampus. Reduced neurogenesis has been shown in healthy rats exposed to stress, but it has not yet been demonstrated in depressed patients. Emerging studies now indicate that selective serotonin reuptake inhibitors can, exert behavioral effects without affecting neurogenesis in mice.

Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a gene-environment rat model of depression.

An animal model of depression combining genetic vulnerability and early-life stress (ELS) was prepared by submitting the Flinders Sensitive Line (FSL) rats to a standard paradigm of maternal separation. We analysed hippocampal synaptic transmission and plasticity in vivo and ionotropic receptors for glutamate in FSL rats, in their controls Flinders Resistant Line (FRL) rats, and in both lines subjected to ELS. A strong inhibition of long-term potentiation (LTP) and lower synaptic expression of NR1 subunit of the NMDA receptor were found in FSL rats.

Acute stress differentially affects corticotropin-releasing hormone mRNA expression in the central amygdala of the "depressed" flinders sensitive line and the control flinders resistant line rats.

Preclinical and clinical evidence suggests that neuropeptides play a role in the pathophysiology of mood disorders. In the present study, we investigated the involvement of the peptides corticotropin-releasing hormone (CRH), neuropeptide Y (NPY) and nociceptin/orphanin FQ (N/OFQ) and of their receptors in the regulation of emotional behaviours. In situ hybridization experiments were performed in order to evaluate the mRNA expression levels of these neuropeptidergic systems in limbic and limbic-related brain regions of the Flinders Sensitive Line (FSL) rats, a putative genetic animal model of depression.

Search for biological correlates of depression and mechanisms of action of antidepressant treatment modalities. Do neuropeptides play a role?

Dysregulation of the monoaminergic systems is likely a sufficient but not a necessary cause of depression. A wealth of data indicates that neuropeptides, e.g.

Chronic amphetamine treatment reduces NGF and BDNF in the rat brain.

Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and noradrenergic agonists and are highly addictive drugs with neurotoxic effect on the brain. In human subjects, it has also been observed that amphetamine causes psychosis resembling positive symptoms of schizophrenia. Neurotrophins are molecules involved in neuronal survival and plasticity and protect neurons against (BDNF) are the most abundant neurotrophins in the central nervous system (CNS) and are important survival factors for cholinergic and dopaminergic neurons.

The effects of social isolation on neuropeptide Y levels, exploratory and anxiety-related behaviors in rats.

NPY is one of the most abundantly expressed peptides within the CNS, and has been previously demonstrated to be altered in several animal models of depression, as well as to be differentially regulated by acute and repeated stress. The effect of social deprivation, through isolation housing, on brain NPY concentrations in adult rats has not been previously investigated. The effects of 12 weeks of social isolation, in adult rats, on anxiety-related behaviors and central concentrations of NPY in: hypothalamus, amygdala, caudate-putamen, hippocampus, and frontal cortex were evaluated.

Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression.

In order to study the gene-environment interaction as well as investigate prophylactic/ameliorative effects of early intervention on development of adult life psychopathology, we superimposed maternal separation on an animal model of depression the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL) rats and studied behavior following treatment with escitalopram. Animals were maternally separated for 180 min/day from postnatal day 2 (PND 2) to 14. The control groups were left undisturbed.

Increased CRF-like and NPY-like immunoreactivity in adult rats exposed to nicotine during adolescence: relation to anxiety-like and depressive-like behavior.

Objective: Recently, animal models have been developed that demonstrate that adolescent nicotine exposure produces neurobehavioral changes which persist into adulthood. This study further examined the impact of adolescent nicotine exposure on anxiety-like and depressive-like behavior, as well as on levels of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) in this model.

Methods: Male adolescent rats (35-40 days old) were administered nicotine using Nicoderm CQ patches (Smith-Kline Beecham).

Neuropeptide y in euthymic lithium-treated women with bipolar disorder.

Plasma neuropeptide Y-like immunoreactivity (NPY-LI) and platelet cyclic AMP (cAMP) activity were determined in 13 women with bipolar disorder stabilized on lithium (Li) and 12 matched healthy controls. No differences in plasma NPY-LI were found between the two groups. In euthymic Li-treated bipolar patients, there was an inverse correlation between plasma NPY-LI levels and intracellular cAMP in prostaglandin E1-stimulated platelets.

Decreased plasma prolactin release in euthymic lithium-treated women with bipolar disorder.

In order to evaluate the effect of treatment with citalopram (CIT) and lithium (Li) on hormone levels in women with bipolar disorder, morning plasma prolactin (PRL) and cortisol (CORT) were measured in 14 nonmedicated depressed patients, 13 depressed patients responding to CIT treatment, 17 euthymic patients on long-term Li treatment, and 11 healthy controls. Plasma PRL values in the Li group were significantly lower than those of the three other groups, suggesting a net inhibitory impact of augmentative effects of Li on dopaminergic activity and serotonergic neurotransmission in the central nervous system. Plasma CORT values in nonmedicated depressed patients were significantly higher than those of healthy controls, indicating hyperactivity of the hypothalamic-pituitary-adrenal system in depression, which appears to be a state-dependent phenomenon, and is normalized upon successful treatment with Li and CIT.

Calcium homeostasis in long-term lithium-treated women with bipolar affective disorder.

The authors investigated the effect of long-term lithium administration on intracellular calcium mobilization. The subjects were 13 women with bipolar affective disorder stabilized on lithium and 12 matched healthy controls. Total and ionized serum calcium, intracellular calcium ion concentration, plasma parathyroid hormone (PTH) and tyrotropin (TSH), serum electrolytes and cyclic AMP (cAMP) activity in platelets were measured.