Altered neurotransmission in brains of autoimmune mice: pharmacological and neurochemical evidence.

Depressive-like behavior is the most profound manifestation of autoimmunity-associated behavioral syndrome in lupus-prone MRL-lpr mice. This led to the hypothesis that chronic autoimmunity and inflammation alter the activity of central serotonergic and dopaminergic systems. Three drugs with a selective mode of action were used to probe the functional status of these two systems in vivo.

Central monoamine and plasma corticosterone changes induced by a bacterial endotoxin: sensitization and cross-sensitization effects.

Low doses of lipopolysaccharide, tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or exposure to a stressor (restraint) increased plasma corticosterone levels. In animals pretreated with lipopolysaccharide, a marked sensitization of the corticosterone response was evident upon subsequent exposure to lipopolysaccharide, TNF-alpha, or restraint, 1 day later. As well, the sickness-inducing effects of lipopolysaccharide, TNF-alpha and IL-1 beta were markedly increased in mice pretreated with lipopolysaccharide.

Central monoamine activity following acute and repeated systemic interleukin-2 administration.

Interleukin-2 (IL-2), together with other cytokines, may be involved in communication between the immune system and the CNS. Moreover, IL-2 alterations have been implicated in psychiatric disorders, and IL-2 immunotherapy may engender neuropsychiatric and cognitive disturbances. Given the presumed relationship between mood disturbances and monoamine activity, the present investigation was undertaken to determine the central monoamine alterations associated with acute and repeated systemic IL-2 administration in mice.

Influence of acute and repeated interleukin-2 administration on spatial learning, locomotor activity, exploratory behaviors, and anxiety.

Interleukin-2 (IL-2), released from activated T cells, influences central neurochemical functioning, and IL-2 immunotherapy in cancer patients may provoke neuropsychiatric and cognitive disturbances. In this study, acute, systemic IL-2 did not influence Morris water-maze performance in mice. In contrast, chronic IL-2 impaired performance when the position of the escape platform varied over days but was without effect when the platform position was fixed.

Sensitization to the effects of tumor necrosis factor-alpha: neuroendocrine, central monoamine, and behavioral variations.

Consistent with the proposition that cytokines act as immunotransmitters between the immune system and the brain, systemic administration of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha; 1.0-4.0 microg) induced mild illness in CD-1 mice, increased plasma corticosterone concentrations, and altered central norepinephrine, dopamine, and serotonin turnover.

Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects.

Systemic administration of lipopolysaccharide (LPS) induces sickness behaviors, as well as alterations of hypothalamic-pituitary-adrenal functioning commonly associated with stressors. In the present investigation, it was demonstrated that systemic LPS treatment induced a sickness-like behavioral profile (reduced active behaviors, soporific effects, piloerection, ptosis), which appeared to be dependent upon the novelty of the environmental context in which animals were tested. As well, LPS induced anxiogenic-like responses, including decreased time spent in the illuminated portion of a light-dark box, reduced open-arm entries in a plus-maze test, and decreased contact with a novel stimulus object in an open-field situation.

Stressor-induced corticotropin-releasing hormone, bombesin, ACTH and corticosterone variations in strains of mice differentially responsive to stressors.

The effects of brief stressor exposure on hypothalamic-pituitary-adrenal (HPA) functioning was assessed in two strains of mice shown to be differentially responsive to stressors. Mild stress (1 min of cold swim, 20 C) led to marked elevations of plasma ACTH and corticosterone concentrations in the stress-reactive BALB/cByJ and the stress-resistant C57Bl/6ByJ mice. Moreover, it was observed that the strains differed in basal CRH content within the amygdala and the paraventricullar nucleus (PVN).

Influence of interleukin-1beta on exploratory behaviors, plasma ACTH, corticosterone, and central biogenic amines in mice.

Systemic administration of interleukin-1beta (IL-1beta) promoted behavioral changes in an open-field exploratory test. In particular, while the cytokine suppressed locomotor activities, these behaviors were not particularly sensitive to dosage differences. In contrast, dose-dependent biphasic variations that varied over time were evident with respect to the exploration of a novel container.

Effects of interleukin-1beta and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study.

The effects of systemically administered interleukin-1beta (1.0 microg) on in vivo variations of monoamines was assessed in several brain regions. Administration of the cytokine provoked a modest increase of extracellular 5-HIAA and HVA from the nucleus accumbens, and 5-HIAA from the hippocampus.

Time-dependent in vivo mesolimbic dopamine variations following antigenic challenge.

Administration of sheep red blood cells (SRBC: 5 x 10(6)) to rats provoked an immune response which peaked 4 days following inoculation. Immune activation elicited an increase of in vivo extracellular dopamine (DA) in the nucleus accumbens, indicating increased release of DA from neurons. The DA alterations coincided with the time of the peak immune response, being significantly altered 4 days after inoculation, and declining to control levels thereafter.

L-tryptophan decreases the breaking point under a progressive ratio schedule of intravenous cocaine reinforcement in the rat.

L-Tryptophan (100 mg/kg, IP), the serotonin [5-hydroxytryptamine (5-HT)] amino acid precursor, significantly reduced the mean breaking point maintained under a self-administration progressive ratio schedule of IV cocaine reinforcement (0.6 mg/injection). This effect was produced over the 5 days of self-administration following treatment.

MDL 72222, ketanserin, and methysergide pretreatments fail to alter breaking points on a progressive ratio schedule reinforced by intravenous cocaine.

The effects of three serotonin [5-hydroxytryptamine (5-HT)] receptor antagonists on cocaine self-administration behavior were investigated. Specifically, the effects of MDL 72222 (a specific 5-HT3 receptor antagonist), ketanserin (a specific 5HT2 receptor antagonist), and methysergide (an aselective 5-HT1/5-HT2 receptor antagonist) on the breaking points reached by rats on a progressive ratio schedule for cocaine reinforcement were examined. Pretreatments with MDL 72222 (7.