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Leishmaniasis is a vectorborne disease caused by Leishmania protozoa, which is a major health problem and a neglected disease common in many regions of the world. Leishmania is an intracellular parasite transmitted by sand flies that causes clinical manifestations ranging from a severe and potentially fatal disease named visceral leishmaniasis to less severe but in many cases disfiguring diseases that mainly affect the skin or mucosal tissues, known as cutaneous leishmaniasis. Despite the detection of Leishmania parasites in the brain and cerebrospinal fluid of human patients and dogs, epidemiological data, as well as information about the mechanisms of central and peripheral nervous system alterations, are poorly described. This review is focused on the current knowledge about the neurological manifestations and immunopathogenic mechanisms in human patients and animals infected with Leishmania. [ABSTRACT FROM AUTHOR]

Receptor antagonist and knockout studies have demonstrated that blockade of signalling via nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) has antidepressant-like effects in mice submitted to the forced swimming test (FST). The aim of the present study was to explore further the antidepressant-like properties of the NOP antagonist UFP-101 in different species (mouse and rat) and using different assays [FST and tail suspension test (TST)], and to investigate the mechanism(s) involved in its actions. UFP-101 (10 nmol i.c.v.) reduced immobility time of Swiss mice in the TST (mean±SEM) from 179±11 to 111±10 s. N/OFQ (1 nmol i.c.v.) was without effect per se, but fully prevented the effect of UFP-101. The spontaneous immobility time of NOP-/- CD1-C57BL/6J-129 mice in the TST was much lower than that of wild-type (NOP+/+) littermates (75±11 vs. 144±17 s) or of Swiss mice. UFP-101 (10 nmol i.c.v.) decreased immobility time (-65%) and increased climbing time (71%) in rats submitted to the FST. In rat brain slices, N/OFQ (100 nM) triggered robust K+-dependent hyperpolarizing currents in locus coeruleus and dorsal raphe neurons. UFP-101 (3 µM) fully prevented N/OFQ-induced currents, but was inactive per se. Fluoxetine, desipramine (both 30 mg/kg i.p.) and UFP-101 (10 nmol i.c.v.) reduced immobility time of mice in the FST. The serotonin synthesis inhibitor p-chlorophenylalanine methylester (PCPA, 4×100 mg/kg per day i.p.) prevented the antidepressant-like effects of fluoxetine and UFP-101 (but not desipramine), whereas N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, neurotoxic for noradrenergic neurons; 50 mg/kg i.p., 7 days beforehand), suppressed only the effect of desipramine. Neither pretreatment affected spontaneous immobility time per se. Thus, UFP-101 exhibits pronounced antidepressant-like effects in different species and animal models, possibly by preventing the inhibitory effects of endogenous N/OFQ on brain monoaminergic (in particular serotonergic) neurotransmission. Participation of the N/OFQ-NOP receptor system in mood modulation sets new potential targets for antidepressant drug development. [ABSTRACT FROM AUTHOR]