introduction: epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. lateral hypothalamus, as the main niche of orexin neurons ...

Orexin receptors belong to the big family of G protein coupled receptors (GPCRs) that constitute the main targets in the modern pharmacological approaches. Although the orexinergic system is involved in a variety of processes, treating sleep-wakefulness disorders such as narcolepsy and insomnia, remains the main therapeutic implication of targeting orexinergic receptors. After novel advances, s...

Orexinergic neurones in the perifornical lateral hypothalamus project to structures of the midbrain, including the substantia nigra and the mesopontine tegmentum. These areas contain the mesencephalic locomotor region (MLR), and the pedunculopontine and laterodorsal tegmental nuclei (PPN/LDT), which regulate atonia during rapid eye movement (REM) sleep. Deficiencies of the orexinergic system re...

Depression is an affective disorder characterized, in particular in its more severe form, i.e., major depressive disorder (MDD), by persistent symptoms of unpleasant (dysphoric) mood, inability to experience pleasure (anhedonia), and a generalized loss of interest in most or all normal activities [1]. Depression is often associated with physiological and cognitive symptoms. Physiological sympto...

The nuclear receptors REV-ERBα and REV-ERBβ are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes. The circadian rhythm is an endogenous mechanism, which generates entrainable biological changes that follow a 24-hour period. It regulates a number of physiological processes, including sleep/wakeful cycles and feeding behaviors...

Neurophysiologic data suggest that orexin neurons are directly excited by ATP through purinergic receptors (P2XR). Anatomical studies, though reporting P2XR in the hypothalamus, did not describe it in the perifornical hypothalamic area, where orexinergic neurons are located. Here we report the presence of the P2X(2)R subunit in the rat perifornical hypothalamus and demonstrate that hypothalamic...

The mesolimbic reward pathway arising from dopaminergic (DA) neurons of the ventral tegmental area (VTA) has been strongly implicated in reward processing and drug abuse. In rodents, behaviors associated with this projection are profoundly influenced by an orexinergic input from the lateral hypothalamus to the VTA. Because the existence and significance of an analogous orexigenic regulatory mec...